Updated on 2026/06/03

写真a

 
NAKATA Masanobu
 
Organization
Research Field in Dentistry, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Health Research Course Developmental Medicine Professor
Title
Professor
Degree
(2001.3 Osaka University)

Research Interests

  • Bacteriology

Research Areas

Oral pathobiological science

Research History

  • 2020.7    Kagoshima University   Research Field in Dentistry, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Health Research Course Developmental Medicine   Professor

Professional Memberships

  • 2008.6    歯科基礎医学会

  • 2007.1    日本細菌学会

  •    JAPANESE ASSOCIATION FOR ORAL BIOLOGY

  •    JAPANESE SOCIETY FOR BACTERIOLOGY

  •    American Society for Microbiology

 

Papers

  • Katsuki Takebe, Shuhei Miyakawa, Takeshi Sangawa, Mamoru Suzuki, Airi Matsumoto, Yuichi Oogai, Masaya Yamaguchi, Tomoko Sumitomo, Kaori Fukuzawa, Shigetada Kawabata, Masanobu Nakata .  Combined structural and FMO-based insights into shaft pilin polymerization mechanism in Streptococcus sanguinis .  International Journal of Biological Macromolecules332 ( Pt 2 ) 148264 - 148264   2025.12Reviewed

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.ijbiomac.2025.148264

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  • Yumika Tanaka, Yuichi Oogai, Airi Matsumoto, Kazuyuki Noguchi, Masanobu Nakata .  The outer membrane autotransporters Fap2 and CmpA facilitate specific coaggregation between Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans serotypes b and d. .  Applied and environmental microbiology91 ( 11 ) e0113225   2025.11Reviewed International coauthorship International journal

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    UNLABELLED: Periodontal disease is a polymicrobial infection in which Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans have been identified as key pathogens associated with disease progression. F. nucleatum is capable of coaggregating with several oral bacterial species, including A. actinomycetemcomitans, and these coaggregations play crucial roles in dental plaque formation. In this study, we investigated the coaggregation properties of both bacteria and identified the molecules that mediate their interaction. Among A. actinomycetemcomitans serotypes a, b, c, d, and g, F. nucleatum strains coaggregated specifically with serotypes b and d. The coaggregation between F. nucleatum and A. actinomycetemcomitans serotype b was significantly suppressed by the addition of lipopolysaccharide (LPS) extracted from A. actinomycetemcomitans serotype b. Among the sugars comprising the O-polysaccharide (O-PS) of serotype b LPS, the addition of N-acetyl-D-galactosamine markedly inhibited their coaggregation. Similarly, the coaggregation between F. nucleatum and A. actinomycetemcomitans serotype d was strongly inhibited by the addition of either the LPS extracted from A. actinomycetemcomitans serotype d or the L-rhamnose present in serotype d O-PS. Furthermore, analysis of outer membrane autotransporter proteins as potential coaggregation factors of F. nucleatum revealed that mutants lacking functional fap2 or cmpA exhibited significantly reduced coaggregation with A. actinomycetemcomitans serotype b or d, respectively. Additionally, we found that these coaggregations significantly promoted biofilm formation during coculture. These findings suggest that the coaggregation between F. nucleatum and A. actinomycetemcomitans serotypes b and d is mediated through interactions between autotransporter proteins and LPSs, thereby contributing to the development of mature biofilms. IMPORTANCE: Fusobacterium nucleatum is a periodontal pathogen that acts as a bridging organism by coaggregating with various oral microbes, including other periodontal pathogens. Recently, this bacterium has been reported to be associated with systemic diseases, including cardiovascular diseases, adverse pregnancy outcomes, and cancer. F. nucleatum possesses numerous adhesins, including autotransporter proteins that are considered to mediate colonization in human tissues. Our study demonstrated that F. nucleatum utilizes two autotransporter proteins (Fap2 and CmpA) to coaggregate with another periodontal pathogen, Aggregatibacter actinomycetemcomitans, through specific interactions with bacterial surface polysaccharides. In addition to the roles of these autotransporters in periodontitis through bacterial coaggregation with other oral bacterial species, our findings potentially provide new insights into the mechanism underlying systemic diseases caused by F. nucleatum binding to host cell carbohydrates and glycoproteins.

    DOI: 10.1128/aem.01132-25

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  • Airi Matsumoto, Yuichi Oogai, Haruka Kurashige, Tomoko Sumitomo, Atsushi Tabata, Masanobu Nakata .  Functional characteristics of membrane vesicles produced by Streptococcus mitis. .  Journal of oral microbiology17 ( 1 ) 2557962 - 2557962   2025Reviewed International journal

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    OBJECTIVE: Mitis group streptococci (MGS) are the predominant oral bacteria that cause bacteremia and infective endocarditis. Although membrane vesicle (MV) secretion has been reported in Streptococcus pneumoniae among MGSs, comprehensive studies using various streptococcal species are limited. We aimed to determine whether MGS species produce MVs and to examine their biological functions. MATERIALS AND METHODS: MVs were isolated from MGS cultures using density gradient ultracentrifugation. The particle sizes of MVs were measured, and proteins in MVs were identified by liquid-chromatography tandem mass spectrometry analysis. Effects of MVs on host cells and oral pathogenic bacteria were investigated. RESULTS: MV production was confirmed in Streptococcus mitis strains NCTC12261, Nm-65, and Nm-76, with particle diameters ranging from 100 to 120 nm. The MVs contained numerous cytoplasmic proteins. The MVs showed internalization into alveolar epithelial cells and induced the production of multiple cytokines, including TNF-α, IL-8, IL-6, IL-1β, and IL-10, in macrophages while suppressing phagocytic activity. In neutrophil-differentiated cells, MVs induced IL-8 but not TNF-α production. MVs from S. pneumoniae TIGR4 and S. mitis Nm-65 inhibited biofilm formation of Aggregatibacter actinomycetemcomitans. CONCLUSIONS: MVs play crucial roles in MGS survival strategies through immune modulation and interspecies competition, contributing to their pathogenicity and host-pathogen interactions.

    DOI: 10.1080/20002297.2025.2557962

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  • Identification of PilX, pilus component of Streptococcus sanguinis .    67 ( 2 ) j.job.2025.100664 - j.job.2025.100664   2025.6Reviewed International coauthorship

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  • Mohammad Farid Ratman, Yuichi Oogai, Airi Matsumoto, Masanobu Nakata .  The ArcAB two-component system is associated with the susceptibility of Aggregatibacter actinomycetemcomitans to superoxide and hydrogen peroxide. .  mSphere10 ( 5 ) e0001925   2025.5Reviewed International coauthorship International journal

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    Aggregatibacter actinomycetemcomitans is a Gram-negative facultative anaerobe and is associated with periodontal disease. This bacterium is exposed to environmental stresses, such as osmotic pressure, temperature shifts, pH shifts, and antimicrobial substances, including reactive oxygen species (ROS), in the human oral cavity. The bacterial two-component system ArcAB modulates gene expression in response to environmental changes, primarily by sensing oxygen pressure in several pathogens belonging to the γ-proteobacteria. It is also known to provide adaptation to ROS stress; however, its function in A. actinomycetemcomitans remains unclear. In this study, we found that the expression of sod, which encodes superoxide dismutase, was increased in the inactivated mutant of arcA, which encodes a response regulator. The mutant exhibited reduced susceptibility to superoxide and hydrogen peroxide (H2O2). Additionally, this strain showed reduced susceptibility to H2O2 from Streptococcus sanguinis and increased survival in macrophages. Since ArcB is the cognate histidine kinase of ArcA, the inactivated mutant of arcB was analyzed for its phenotypes. The arcB mutant exhibited reduced susceptibility to superoxide and H2O2. Compared to wild type, the phosphorylation level of ArcA in the arcB mutant was decreased. These results suggest that the ArcA response regulator receives phosphate groups from ArcB histidine kinase and negatively regulates the expression of sod, thereby affecting bacterial survival in response to ROS produced by oral commensals and host immune cells.IMPORTANCEAggregatibacter actinomycetemcomitans is an oral pathogen that is known to be a highly virulent periodontal pathogen, showing strong adherence to periodontal tissue and toxin production, which leads to aggressive periodontitis. This bacterium is associated not only with oral infections but also with systemic infections, such as infective endocarditis and brain abscesses. Therefore, elucidating the adaptation mechanisms of this bacterium is important for human health. Bacterial two-component systems (TCSs) have been studied as attractive targets for elucidating bacterial fitness and pathogenicity in the host. This study characterized a TCS in A. actinomycetemcomitans, ArcAB, which is associated with susceptibility to ROS produced by host cells or oral commensals. Our findings provide insights into the bacterial adaptation mechanism against oxidative stress, which is crucial for understanding the survival strategies of the periodontal pathogen.

    DOI: 10.1128/msphere.00019-25

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  • Yuichi Oogai, Yumika Tanaka, Masanobu Nakata .  Microbial Coaggregation in the Oral Cavity: Molecular Interactions and Current Insights. .  International journal of molecular sciences26 ( 21 )   2025.10Invited Reviewed International journal

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    Periodontitis is a chronic inflammatory disease of the periodontal tissues primarily caused by dysbiotic bacterial communities. Accumulating evidence suggests that periodontal pathogens not only drive the initiation and progression of periodontitis but also significantly contribute to systemic disorders, including diabetes mellitus, cardiovascular disease, cancer, and adverse pregnancy outcomes, such as preterm birth. The key periodontal pathogens implicated in disease pathogenesis include Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum. Among the diverse factors governing bacterial colonization and biofilm formation, interspecies interactions, particularly coaggregation, play a critical role in dental plaque maturation and the establishment of pathogenic microbial communities. Coaggregation facilitates the spatial organization of bacteria within biofilms, enhances bacterial survival, and modulates virulence factor expression. This review summarizes current knowledge regarding bacterial interactions involving major periodontal pathogens, with particular emphasis on coaggregation mechanisms, and discusses the implications of this coaggregation for periodontitis pathogenesis and associated systemic diseases.

    DOI: 10.3390/ijms262110552

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  • Miura Kouki, Matsumoto Airi, Oogai Yuichi, Nakata Masanobu, Nishitani Yoshihiro .  抗微生物能を有する新規な歯科材料としてのキトサンの応用 形状、分子量、脱アセチル化度がCandida albicansへの抗微生物活性に与える影響(Application of chitosan as a novel antimicrobial dental material: Effects of form, molecular weight, and deacetylation degree on its antimicrobial activity against Candida albicans) .  Dental Materials Journal44 ( 5 ) 497 - 506   2025.10

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    Language:English   Publisher:(一社)日本歯科理工学会  

    キトサンを抗微生物性の歯科材料として用いCandida albicans治療に役立てる可能性について検討した。ズワイガニ(Chionoecetes opilio)およびイカ(分類学上は十腕形上目)から精製されたキトサンの製品を4種入手した。そのキトサン4製品では分子量と脱アセチル化度がそれぞれ異なっていた。抗微生物活性を評価する手法には、真菌生存アッセイ、培養濁度測定法、生細胞/死細胞染色法を使用した。どのキトサン製品も抗微生物活性を示したが、その有効性はイカ由来の製品の方がより良好であった。分子量がより高いことは、作用が即時に生じることと相関していた。また、脱アセチル化度がより高いことは活性持続と相関していた。C.albicansをキトサンで処理すると細胞外にあるATPと活性酸素種の濃度は上昇し、ミトコンドリア生合成および薬剤耐性に関係する遺伝子の発現は抑制された。以上から、キトサンは、口腔カンジダ症を予防・治療する目的で歯科材料に配合する抗微生物剤として利用できる可能性が示唆された。

  • MIURA Kouki, MATSUMOTO Airi, OOGAI Yuichi, NAKATA Masanobu, NISHITANI Yoshihiro .  Application of chitosan as a novel antimicrobial dental material —Effects of form, molecular weight, and deacetylation degree on its antimicrobial activity against <i>Candida albicans</i> .  Dental Materials Journal44 ( 5 ) 497 - 506   2025.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Society for Dental Materials and Devices  

    <p>Oral candidiasis is a significant health concern, especially for elderly individuals. The present study examined chitosan as a potential antimicrobial dental material for <i>Candida albicans</i> treatment. Four types of chitosan products purified from <i>Chionoecetes opilio</i> and Decapodiformes, with varying weight average molecular weight and degree of deacetylation (DAC) were used. Antimicrobial activity was assessed with fungal viability assays, culture turbidity measurements, and live/dead cell staining, while mechanism of action was determined by examining extracellular adenosine triphosphate (ATP) level, reactive oxygen species (ROS) production, and gene expression changes. All examined products exhibited antimicrobial activity, with Decapodiformes-derived chitosan showing better efficacy. Greater molecular weight was correlated with immediate effects and higher DAC with sustained activity. Chitosan treatment increased extracellular ATP and ROS levels, and suppression of genes involved in mitochondrial biosynthesis and drug resistance. These findings suggest potential use of chitosan as an antimicrobial agent in dental materials for oral candidiasis prevention and treatment.</p>

    DOI: 10.4012/dmj.2024-372

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    CiNii Research

  • Li Yixuan, Masanobu Nakata, Hirono Migita, Airi Matsumoto, Yuichi Oogai, Katsuki Takebe, Masaya Yamaguchi, Nobuo Okahashi, Tomoko Sumitomo, Shigetada Kawabata .  Identification of PilX, pilus component of Streptococcus sanguinis .  Journal of Oral Biosciences67 ( 2 ) 100664 - 100664   2025.4

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.job.2025.100664

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  • Yuki Takahara, Tomoko Sumitomo, Masamitsu Kono, Moe Takemura, Yukako Akamatsu, Yujiro Hirose, Masaya Yamaguchi, Masanobu Nakata, Muneki Hotomi, Shigetada Kawabata .  Pneumolysin contributes to dysfunction of nasal epithelial barrier for promotion of pneumococcal dissemination into brain tissue .  mSphere9 ( 10 ) e0065524   2024.9

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:American Society for Microbiology  

    ABSTRACT

    Streptococcus pneumoniae is one of the major pathogens responsible for bacterial meningitis and neurological sequelae. The present study was conducted to identify a non-hematogenous route used by S. pneumoniae to gain access to brain tissue without causing bacteremia or pneumonia, as well as bacterial and host factors involved in this process. To investigate the molecular mechanisms and dissemination pathways of pneumococcal infection in brain tissue, mice were intranasally inoculated with S. pneumoniae strain EF3030, a clinical isolate from a patient with otitis media. Pneumococci were isolated from the frontal olfactory bulb, caudal cerebrum, and cerebellum, with neither bacteremia nor pneumonia observed in the present model. Immunostaining imaging revealed the presence of S. pneumoniae organisms in olfactory nerve fibers. Knockout of the ply gene encoding pneumolysin (PLY) markedly compromised the ability of the bacterial organisms to disseminate into brain tissue, whereas the dissemination efficiency of the complemented strain was restored to nearly the same level as the wild type. Notably, distinct upregulation of Gli1 and Snail1, which are involved in the transcriptional repression of junctional proteins, along with downregulation of E-cadherin, was detected in nasal lavage samples from mice infected with the wild-type or complemented strain, but not in those from mice infected with the ply mutant. Taken together, the present findings indicate that PLY induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, thus allowing pneumococcal dissemination to brain tissue that occurs in a non-hematogenous manner.

    IMPORTANCE

    Bacterial meningitis, considered to be caused by bacteremia, can lead to blood–brain barrier disruption and bacterial dissemination into the central nervous system. Despite the availability of intravenously administered antibiotics with cerebrospinal fluid transferability, bacterial meningitis remains associated with high rates of morbidity and mortality. Here, we utilized Streptococcus pneumoniae strain EF3030, clinically isolated from otitis media, for the construction of a murine infection model to investigate the molecular mechanisms by which nasally colonized pneumococci disseminate into brain tissue. The obtained findings indicate that pneumolysin (PLY) induces Gli1-Snail1-dependent dysfunction of the nasal epithelial barrier, which facilitates pneumococcal dissemination to brain tissue in a non-hematogenous manner. Our results support the existence of an alternative route by which S. pneumoniae can reach the central nervous system and indicate the need for the development of novel therapeutic strategies, which would be an important contribution to the clinical management of bacterial meningitis.

    DOI: 10.1128/msphere.00655-24

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  • Talat Dalia, Sumitomo Tomoko, Honda-Ogawa Mariko, Takahara Yuki, Mori Yasushi, Yamaguchi Masaya, Nakata Masanobu, Ibrahim Madiha S., Kawabata Shigetada .  肺炎球菌性肺炎の病態形成に関係する血清型4の株が有する二成分制御系のTCS08(Two-component regulatory system TCS08 of a serotype 4 strain in pneumococcal pneumonia pathogenesis) .  Journal of Oral Biosciences66 ( 3 ) 567 - 574   2024.9

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    肺炎球菌が持つ二成分制御系TCS08による、細菌の定着、肺炎の発症、肺の機能障害への寄与について検討した。マウス実験では、肺炎球菌由来のTCS08は気道への細菌定着に関与していることが示された。血清型が4型の肺炎球菌臨床分離株であるTIGR4株を材料とし、TCS08のシグナル伝達経路を途絶させるためにhk08遺伝子をノックアウトした。その結果、それに感染させたマウスの生存性は悪化し気道内の細菌量は増加した。野生株または相補株の菌と比較した場合、hk08ノックアウト株の菌に感染させたマウスの肺組織には大量の炎症細胞の浸潤、浮腫形成、び漫性肺胞傷害が認められた。同ノックアウト株では莢膜産生、鎖長の延長、表面に出現する蛋白質のプロファイルといった病原性に関連する表現型が変化していた。TCS08は肺炎球菌の気道環境への適応を補佐することで同菌の定着と肺の機能障害に寄与し、ついには肺炎を発症させることが明らかになった。

  • 山口 雅也, 東 孝太郎, 武部 克希, 中田 匡宣, 住友 倫子, 川端 重忠 .  Structural analysis of inactive hyaluronidase of Streptococcus pyogenes(タイトル和訳中) .  日本細菌学雑誌79 ( 2 ) 268 - 268   2024.7

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  • Dalia Talat, Tomoko Sumitomo, Mariko Honda-Ogawa, Yuki Takahara, Yasushi Mori, Masaya Yamaguchi, Masanobu Nakata, Madiha S. Ibrahim, Shigetada Kawabata .  Two-component regulatory system TCS08 of a serotype 4 strain in pneumococcal pneumonia pathogenesis .  Journal of Oral Biosciences66 ( 3 ) 567 - 574   2024.6

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.job.2024.06.001

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  • Katsuki Takebe, Mamoru Suzuki, Takeshi Sangawa, Bernd Kreikemeyer, Masaya Yamaguchi, Narikazu Uzawa, Tomoko Sumitomo, Shigetada Kawabata, Masanobu Nakata .  Analysis of FctB3 crystal structure and insight into its structural stabilization and pilin linkage mechanisms .  Archives of Microbiology206 ( 1 ) 4   2023.11

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1007/s00203-023-03727-1

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    Other Link: https://link.springer.com/article/10.1007/s00203-023-03727-1/fulltext.html

  • Takebe K, Suzuki M, Sangawa T, Kreikemeyer B, Yamaguchi M, Uzawa N, Sumitomo T, Kawabata S, Nakata M. .  Analysis of FctB3 crystal structure and insight into its structural stabilization and pilin linkage mechanisms. .  Archives in Microbiology   2023.11Reviewed International coauthorship

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    DOI: 10.1007/s00203-023-03727-1.

  • 武部 克希, 鈴木 守, 東 孝太郎, 山口 雅也, 住友 倫子, 川端 重忠, 中田 匡宣 .  Streptococcus sanguinisが産生する線毛タンパク質のX線結晶構造解析 .  Journal of Oral Biosciences Supplement2023   [P1 - 25]   2023.9

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    Language:Japanese   Publisher:(一社)歯科基礎医学会  

  • Kubota Seiko, Nakata Masanobu, Hirose Yujiro, Yamaguchi Masaya, Kreikemeyer Bernd, Uzawa Narikazu, Sumitomo Tomoko, Kawabata Shigetada .  転写調節因子のメッセンジャーRNAレベルの調節を介した化膿レンサ球菌M49株による線毛産生におけるリボヌクレアーゼYの関与(Involvement of ribonuclease Y in pilus production by M49 Streptococcus pyogenes strain via modulation of messenger RNA level of transcriptional regulator) .  Microbiology and Immunology67 ( 7 ) 319 - 333   2023.7

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    Language:English   Publisher:John Wiley & Sons Australia, Ltd  

    Nra転写調節因子を有する化膿レンサ球菌M49型菌株による温度感受性線毛産生にCvfA(RNaseY)が果たす役割を調べた。線毛関連遺伝子を抑制するノンコーディング(nc)RNAであるfasXとcovRの発現レベル、CovRのリン酸化レベルに及ぼす培養温度の影響を調べた。cvfA欠失が、β溶血性やSpeBカゼイン分解活性などのビルレンス関連表現型、ならびにヒト血液中の生存に及ぼす影響を調べた。cvfA欠失株(ΔcvfA)を用いた発現解析により、cvfA欠失はFCT3型菌株の線毛産生を減少させることが示された。線毛産生の減少はnra mRNAとNraタンパク質のレベル低下により引き起こされ、CovR調節因子またはfasX ncRNAに起因するものではないことが示された。線毛減少はヒト角化細胞株HaCaT細胞へのΔcvfAの付着量減少を引き起こした。予想外なことに、fasX発現が温度感受性であることが判明した。ΔcvfAの表現型分析により、培養温度とcvfA欠失はストレプトリジンS(SLS)とシステインプロテアーゼSpeB活性に様々な影響を及ぼすことが判明した。特に25℃においてcvfA欠失はspeB mRNAレベルとSpeB活性を低下させた。一方、ΔcvfAのSLSコーディング遺伝子sagAのmRNAレベルは25℃で低下したがcvfA欠失により溶血活性は上昇した。

  • Seiko Kubota, Masanobu Nakata, Yujiro Hirose, Masaya Yamaguchi, Bernd Kreikemeyer, Narikazu Uzawa, Tomoko Sumitomo, Shigetada Kawabata .  Involvement of ribonuclease Y in pilus production by M49 Streptococcus pyogenes strain via modulation of messenger RNA level of transcriptional regulator. .  Microbiology and immunology67 ( 7 ) 319 - 333   2023.5International journal

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    Streptococcus pyogenes displays a wide variety of pili, which is largely dependent on serotype. A distinct subset of S. pyogenes strains that possess the Nra transcriptional regulator demonstrates thermoregulated pilus production. Findings obtained in the present study of an Nra-positive serotype M49 strain revealed involvement of conserved virulence factor A (CvfA), also referred to as ribonuclease Y (RNase Y), in virulence factor expression and pilus production, while a cvfA deletion strain showed reduced pilus production and adherence to human keratinocytes as compared with wild-type and revertant strains. Furthermore, transcript levels of pilus subunits and srtC2 genes were decreased by cvfA deletion, which was remarkable at 25°C. Likewise, both messenger RNA (mRNA) and protein levels of Nra were remarkably decreased by cvfA deletion. Whether the expression of other pilus-related regulators, including fasX and CovR, was subject to thermoregulation was also examined. While the mRNA level of fasX, which inhibits cpa and fctA translation, was decreased by cvfA deletion at both 37°C and 25°C, CovR mRNA and protein levels, as well as its phosphorylation level were not significantly changed, suggesting that neither fasX nor CovR is necessarily involved in thermosensitive pilus production. Phenotypic analysis of the mutant strains revealed that culture temperature and cvfA deletion had varied effects on streptolysin S and SpeB activities. Furthermore, bactericidal assay data showed that cvfA deletion decreased the rate of survival in human blood. Together, the present findings indicate that CvfA is involved in regulation of pilus production and virulence-related phenotypes of the serotype M49 strain of S. pyogenes.

    DOI: 10.1111/1348-0421.13069

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  • Seiko Kubota, Masanobu Nakata, Yujiro Hirose, Masaya Yamaguchi, Bernd Kreikemeyer, Narikazu Uzawa, Tomoko Sumitomoa, Shigetada Kawabata .  Involvement of ribonuclease Y in pilus production by M49 Streptococcus pyogenes strain via modulation of mRNA level of transcriptional regulator .  Microbiology and Immunology   2023Reviewed International coauthorship

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

  • Nobuo Okahashi, Masanobu Nakata, Hirotaka Kuwata, Shigetada Kawabata .  Oral mitis group streptococci: a silent majority in our oral cavity .  Microbiology and Immunology66 ( 12 ) 539 - 551   2022.9

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1111/1348-0421.13028

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  • Nakazono K, Le MN, Kawada-Matsuo M, Kimheang N, Hisatsune J, Oogai Y, Nakata M, Nakamura N, Sugai M, Komatsuzawa H. .  Complete sequences of epidermin and nukacin encoding plasmids from oral-derived Staphylococcus epidermidis and their antibacterial activity. .  PLoS One17 ( 1 ) e0258283   2022Reviewed

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    DOI: 10.1371/journal.pone.0258283.

  • Okahashi N, Sumitomo T, Nakata M, Kawabata S. .  Secondary streptococcal infection following influenza. .  Microbiol Immunol.   2022Reviewed

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    DOI: 10.1111/1348-0421.12965.

  • Takemura, M., Yamaguchi, M., Kobayashi, M., ...Uzawa, N., Kawabata .  Pneumococcal BgaA Promotes Host Organ Bleeding and Coagulation in a Mouse Sepsis Model .      2022Reviewed

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  • Nobuo Okahashi, Tomoko Sumitomo, Masanobu Nakata, Hirotaka Kuwata, Shigetada Kawabata .  Oral mitis group streptococci reduce infectivity of influenza A virus via acidification and H2O2 production. .  PloS one17 ( 11 ) e0276293   2022International journal

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    Members of the mitis group streptococci are the most abundant inhabitants of the oral cavity and dental plaque. Influenza A virus (IAV), the causative agent of influenza, infects the upper respiratory tract, and co-infection with Streptococcus pneumoniae is a major cause of morbidity during influenza epidemics. S. pneumoniae is a member of mitis group streptococci and shares many features with oral mitis group streptococci. In this study, we investigated the effect of viable Streptococcus oralis, a representative member of oral mitis group, on the infectivity of H1N1 IAV. The infectivity of IAV was measured by a plaque assay using Madin-Darby canine kidney cells. When IAV was incubated in growing culture of S. oralis, the IAV titer decreased in a time- and dose-dependent manner and became less than 100-fold, whereas heat-inactivated S. oralis had no effect. Other oral streptococci such as Streptococcus mutans and Streptococcus salivarius also reduced the viral infectivity to a lesser extent compared to S. oralis and Streptococcus gordonii, another member of the oral mitis group. S. oralis produces hydrogen peroxide (H2O2) at a concentration of 1-2 mM, and its mutant deficient in H2O2 production showed a weaker effect on the inactivation of IAV, suggesting that H2O2 contributes to viral inactivation. The contribution of H2O2 was confirmed by an inhibition assay using catalase, an H2O2-decomposing enzyme. These oral streptococci produce short chain fatty acids (SCFA) such as acetic acid as a by-product of sugar metabolism, and we also found that the inactivation of IAV was dependent on the mildly acidic pH (around pH 5.0) of these streptococcal cultures. Although inactivation of IAV in buffers of pH 5.0 was limited, incubation in the same buffer containing 2 mM H2O2 resulted in marked inactivation of IAV, which was similar to the effect of growing S. oralis culture. Taken together, these results reveal that viable S. oralis can inactivate IAV via the production of SCFAs and H2O2. This finding also suggests that the combination of mildly acidic pH and H2O2 at low concentrations could be an effective method to inactivate IAV.

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  • Comprehensive characterization of sortase A-dependent surface proteins in Streptococcus mutans .    66 ( 3 ) 145 - 156   2022

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  • 東 孝太郎, 山口 雅也, 中田 匡宣, 武部 克希, 住友 倫子, 鈴木 守, 川端 重忠 .  化膿レンサ球菌の不活性型ヒアルロン酸分解酵素の結晶構造解析と活性型変異体の構造予測(Structural analysis of Streptococcus pyogenes hyaluronidase and in silico analysis based on structural models) .  Journal of Oral Biosciences Supplement2021   181 - 181   2021.10

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  • Sumitomo T, Nakata M, Nagase S, Takahara Y, Honda-Ogawa M, Mori Y, Akamatsu Y, Yamaguchi M, Okamoto S, Kawabata S .  GP96 drives exacerbation of secondary bacterial pneumonia following influenza A virus infection .  mBio   e0326920   2021.6Reviewed

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    DOI: 10.1128/mBio.03269-20

  • Expression of virulence factors under different environmental conditions in Aggregatibacter actinomycetemcomitans .    65 ( 3 ) 101 - 114   2021.3

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  • 東 孝太郎, 山口 雅也, 中田 匡宣, 武部 克希, 住友 倫子, 鈴木 守, 川端 重忠 .  微生物の分子論(遺伝子・タンパク質・情報伝達・代謝・各種オミクス等) 結晶構造解析に基づく化膿レンサ球菌におけるヒアルロン酸分解酵素の分子機構解明 .  日本細菌学雑誌76 ( 1 ) 53 - 53   2021.2

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  • Hirose, Y., Yamaguchi, M., Sumitomo, T., Nakata, M., Hanada, T., Okuzaki, D., Motooka, D., Mori, Y., Kawasaki, H., Coady, A., Uchiyama, S., Hiraoka, M., Zurich, R., Riestra, A., Amagai, M., Nizet, V., Kawabata, S. .  Streptococcus pyogenes upregulates arginine catabolism to exert its pathogenesis on the skin surface. .  Cell Reports34 ( 13 ) 108924   2021Invited Reviewed International coauthorship

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    DOI: 10.1016/j.celrep.202

  • Nakata, M, Kreikemeyer, B .  Genetics, Structure, and Function of Group A Streptococcal Pili .  Frontiers in Microbiology12   616508   2021

  • Ayumi Fujita, Yuichi Oogai, Miki Kawada-Matsuo, Masanobu Nakata, Kazuyuki Noguchi, Hitoshi Komatsuzawa .  Expression of virulence factors under different environmental conditions in Aggregatibacter actinomycetemcomitans .  Microbiology and Immunology65 ( 3 ) 101 - 114   2021Reviewed International journal

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    Aggregatibacter actinomycetemcomitans is a facultative anaerobic Gram-negative bacterium associated with periodontal diseases, especially aggressive periodontitis. The virulence factors of this pathogen, including adhesins, exotoxins, and endotoxin, have been extensively studied. However, little is known about their gene expression mode in the host. Herein, we investigated whether culture conditions reflecting in vivo environments, including serum and saliva, alter expression levels of virulence genes in the strain HK1651, a JP2 clone. Under aerobic conditions, addition of calf serum (CS) into a general medium induced high expression of two outer membrane proteins (omp100 and omp64). The high expression of omp100 and omp64 was also induced by an iron-limited medium. RNA-seq analysis showed that the gene expressions of several factors involved in iron acquisition were increased in the CS-containing medium. When HK1651 was grown on agar plates, genes encoding many virulence factors, including the Omps, cytolethal distending toxin, and leukotoxin, were differentially expressed. Then, we investigated their expression in five other A. actinomycetemcomitans strains grown in general and CS-containing media. The expression pattern of virulence factors varied among strains. Compared with the other five strains, HK1561 showed high expression of omp29 regardless of the CS addition, while the gene expression of leukotoxin in HK1651 was higher only in the medium without CS. HK1651 showed reduced biofilm in both CS- and saliva-containing media. Coaggregation with Fusobacterium nucleatum was remarkably enhanced using HK1651 grown in the CS-containing medium. Our results indicate that the expression of virulence factors is altered by adaptation to different conditions during infection.

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  • Katsumata T, Nguyen-Tra Le M, Kawada-Matsuo M, Taniguchi Y, Ouhara K, Oogai Y, Nakata M, Mizuno N, Nishitani Y, Komatsuzawa H. .  Comprehensive characterization of sortase A-dependent surface proteins in Streptococcus mutans. .  Microbiol Immunol.   2021

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  • Oogai Y, Nakata M. .  Small regulatory RNAs of oral streptococci and periodontal bacteria. .  Jpn Dent Sci Rev. 57   209 - 216   2021Invited Reviewed

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    DOI: 10.1016/j.jdsr.2021.09.004.

  • Watanabe A, Kawada-Matsuo M, Le MN, Hisatsune J, Oogai Y, Nakano Y, Nakata M, Miyawaki S, Sugai M, Komatsuzawa H. .  Comprehensive analysis of bacteriocins in Streptococcus mutans. .  Sci Rep.11 ( 1 ) 12963   2021Reviewed

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    DOI: 10.1038/s41598-021-92370-1.

  • Oogai Y, Nakata M. .  Small regulatory RNAs of oral streptococci and periodontal bacteria. .  Jpn. Dent. Sci. Rev.57   209 - 216   2021Invited Reviewed

  • NAKATA Masanobu .  Temperature sensitive translational regulation by Streptococcus pyogenes .      2021Invited Reviewed

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  • Y. Hirose, M. Yamaguchi, T. Sumitomo, M. Nakata, T. Hanada, D. Okuzaki, D. Motooka, Y. Mori, H. Kawasaki, A. Coady, S. Uchiyama, M. Hiraoka, R. Zurich, A. Riestra, M. Amagai, V. Nizet, S. Kawabata .  Streptococcus pyogenes upregulates arginine catabolism to exert its pathogenesis on the skin surface. .  Cell Reports34 ( 13 ) 108924 - 108924   2021Reviewed International journal

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    The arginine deiminase (ADI) pathway has been found in many kinds of bacteria and functions to supplement energy production and provide protection against acid stress. The Streptococcus pyogenes ADI pathway is upregulated upon exposure to various environmental stresses, including glucose starvation. However, there are several unclear points about the advantages to the organism for upregulating arginine catabolism. We show that the ADI pathway contributes to bacterial viability and pathogenesis under low-glucose conditions. S. pyogenes changes global gene expression, including upregulation of virulence genes, by catabolizing arginine. In a murine model of epicutaneous infection, S. pyogenes uses the ADI pathway to augment its pathogenicity by increasing the expression of virulence genes, including those encoding the exotoxins. We also find that arginine from stratum-corneum-derived filaggrin is a key substrate for the ADI pathway. In summary, arginine is a nutrient source that promotes the pathogenicity of S. pyogenes on the skin.

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  • Nobuo Okahashi, Masanobu Nakata, Yujiro Hirose, Hirobumi Morisaki, Hideo Kataoka, Hirotaka Kuwata, Shigetada Kawabata .  Streptococcal H2O2 inhibits IgE-triggered degranulation of RBL-2H3 mast cell/basophil cell line by inducing cell death .  PLOS ONE15 ( 4 ) e0231101 - e0231101   2020.4

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  • Nakata Masanobu, Sumitomo Tomoko, Patenge Nadja, Kreikemeyer Bernd, Kawabata Shigetada .  Thermosensitive pilus production by FCT type 3 Streptococcus pyogenes controlled by Nra regulator translational efficiency .  MOLECULAR MICROBIOLOGY113 ( 1 ) 173 - 189   2020Reviewed International coauthorship

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    DOI: 10.1111/mmi.14408

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  • Hirose Y, Yamaguchi M, Takemoto N, Miyoshi-Akiyama T, Sumitomo T, Nakata M, Ikebe T, Hanada T, Yamaguchi T, Kawahara R, Okuno R, Otsuka H, Matsumoto Y, Terashima Y, Kazawa Y, Nakanishi N, Uchida K, Akiyama Y, Iwabuchi K, Nakagawa C, Yamamoto K, Nizet V, Kawabata S. .  Genetic characterization of Streptococcus pyogenes emm89 strains isolated in Japan from 2011 to 2019. .  Infectious Microbes & Diseases 2 ( 4 ) 160 - 166   2020Reviewed International coauthorship

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  • Yamaguchi M, Takemura M, Higashi K, Goto K, Hirose Y, Sumitomo T, Nakata M, Uzawa N, Kawabata S. .  Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis. .  Frontiers in Microbiology11   582437   2020Reviewed

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  • Nakata Masanobu, Kawabata Shigetada .  Detection of fibronectin-binding proteins of Streptococcus pyogenes by ligand-blot analysis. .  Methods in Molecular Biology (published by Springer Nature)2136   181 - 190   2020Invited Reviewed

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  • Yamaguchi Masaya, Hirose Yujiro, Takemura Moe, Ono Masayuki, Sumitomo Tomoko, Nakata Masanobu, Terao Yutaka, Kawabata Shigetada .  Streptococcus pneumoniae Evades Host Cell Phagocytosis and Limits Host Mortality Through Its Cell Wall Anchoring Protein PfbA .  FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY9   301   2019Invited Reviewed

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    DOI: 10.3389/fcimb.2019.00301

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  • Kazuya Takeda, Shuhei Sakakibara, Kazuo Yamashita, Daisuke Motooka, Shota Nakamura, Marwa Ali El Hussien, Jun Katayama, Yohei Maeda, Masanobu Nakata, Shigeyuki Hamada, Daron M Standley, Masaki Hayama, Takashi Shikina, Hidenori Inohara, Hitoshi Kikutani .  Allergic conversion of protective mucosal immunity against nasal bacteria in patients with chronic rhinosinusitis with nasal polyposis. .  The Journal of allergy and clinical immunology143 ( 3 ) 1163 - 1175   2019Invited Reviewed

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    BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by eosinophilic inflammation and polyposis at the nose and paranasal sinus and a high concentration of IgE in nasal polyps (NPs). The causative antigen and pathogenesis of CRSwNP remain unknown. OBJECTIVE: We aimed to identify reactive allergens of IgE antibodies produced locally in NPs of patients with CRSwNP. We also attempted to unravel the differentiation pathway of IgE-producing B cells in NPs. METHODS: IgE reactivity of patients with CRSwNP was investigated by characterizing single cell-derived mAbs. T-cell response against identified allergens was investigated in vitro. NP-infiltrating lymphocytes were characterized by using flow cytometry. Immunoglobulins expressed in NPs were analyzed by using high-throughput DNA sequencing for immunoglobulin. RESULTS: About 20% of isolated IgE antibodies derived from NP-residing plasmablasts specifically recognized surface determinants of nasal bacteria, such as Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae. A TH2 response against S pyogenes was observed in patients with CRSwNP. Flow cytometric analysis revealed sizable germinal center B-like cell and plasmablast subsets expressing IgE on the cell surface in NPs. High-throughput DNA sequencing immunoglobulin analysis highlighted the clonal connectivity of IgE with IgG and IgA1. The Iε-Cα1 circle transcript was detected in NPs. CONCLUSIONS: In patients with CRSwNP, nasal bacteria-reactive B cells differentiate into IgE-producing B cells through IgG/IgA1-IgE class switching, suggesting that allergic conversion of the mucosal response against nasal bacteria underlies disease pathogenesis.

    DOI: 10.1016/j.jaci.2018.07.006

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  • Yamaguchi Masaya, Goto Kana, Hirose Yujiro, Yamaguchi Yuka, Sumitomo Tomoko, Nakata Masanobu, Nakano Kazuhiko, Kawabata Shigetada .  Identification of evolutionarily conserved virulence factor by selective pressure analysis of Streptococcus pneumoniae .  COMMUNICATIONS BIOLOGY2   96   2019Invited Reviewed

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    DOI: 10.1038/s42003-019-0340-7

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  • Yujiro Hirose, Masaya Yamaguchi, Daisuke Okuzaki, Daisuke Motooka, Hiroshi Hamamoto, Tomoki Hanada, Tomoko Sumitomo, Masanobu Nakata, Shigetada Kawabata .  Streptococcus pyogenes transcriptome changes in the inflammatory environment of necrotizing fasciitis .  Applied and Environmental Microbiology85 ( 21 ) e01428-19   2019Invited Reviewed

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    © 2019 American Society for Microbiology. Streptococcus pyogenes is a major cause of necrotizing fasciitis, a lifethreatening subcutaneous soft-tissue infection. At the host infection site, the local environment and interactions between the host and bacteria have effects on bacterial gene expression profiles, while the gene expression pattern of S. pyogenes related to this disease remains unknown. In this study, we used a mouse model of necrotizing fasciitis and performed RNA-sequencing (RNA-seq) analysis of S. pyogenes M1T1 strain 5448 by isolating total RNA from infected hind limbs obtained at 24, 48, and 96 h postinfection. RNA-seq analysis results identified 483 bacterial genes whose expression was consistently altered in the infected hindlimbs compared to their expression under in vitro conditions. Genes showing consistent enrichment during infection included 306 encoding molecules involved in virulence, carbohydrate utilization, amino acid metabolism, trace-metal transport, and the vacuolar ATPase transport system. Surprisingly, drastic upregulation of 3 genes, encoding streptolysin S precursor (sagA), cysteine protease (speB), and secreted DNase (spd), was noted in the present mouse model (log2 fold change, > 6.0, > 9.4, and > 7.1, respectively). Conversely, the number of consistently downregulated genes was 177, including those associated with the oxidative stress response and cell division. These results suggest that in necrotizing fasciitis, S. pyogenes shows an altered metabolism, decreased cell proliferation, and upregulation of expression of major toxins. Our findings are considered to provide critical information for developing novel treatment strategies and vaccines for necrotizing fasciitis.

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  • Hirose Y, Yamaguchi M, Goto K, Sumitomo T, Nakata M, Kawabata S .  Competence-induced protein Ccs4 facilitates pneumococcal invasion into brain tissue and virulence in meningitis .  Virulence9 ( 1 ) 1576 - 1587   2018.9

  • 東 孝太郎, 武部 克希, 山口 雅也, 住友 倫子, 中田 匡宣, 鈴木 守, 川端 重忠 .  化膿レンサ球菌におけるヒアルロン酸分解酵素の分子系統解析およびタンパク質構造解析 .  Journal of Oral Biosciences Supplement2018   351 - 351   2018.9

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  • Katja Kriebel, Cathleen Hieke, Brigitte Müller-Hilke, Masanobu Nakata, Bernd Kreikemeyer .  Oral biofilms from symbiotic to pathogenic interactions and associated disease - Connection of periodontitis and rheumatic arthritis by peptidylarginine deiminase .  Frontiers in Microbiology9   53   2018.1

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    A wide range of bacterial species are harbored in the oral cavity, with the resulting complex network of interactions between the microbiome and host contributing to physiological as well as pathological conditions at both local and systemic levels. Bacterial communities inhabit the oral cavity as primary niches in a symbiotic manner and form dental biofilm in a stepwise process. However, excessive formation of biofilm in combination with a corresponding deregulated immune response leads to intra-oral diseases, such as dental caries, gingivitis, and periodontitis. Moreover, oral commensal bacteria, which are classified as so-called "pathobionts" according to a now widely accepted terminology, were recently shown to be present in extra-oral lesions with distinct bacterial species found to be involved in the onset of various pathophysiological conditions, including cancer, atherosclerosis, chronic infective endocarditis, and rheumatoid arthritis. The present review focuses on oral pathobionts as commensal and healthy members of oral biofilms that can turn into initiators of disease. We will shed light on the processes involved in dental biofilm formation and also provide an overview of the interactions of P. gingivalis, as one of the most prominent oral pathobionts, with host cells, including epithelial cells, phagocytes, and dental stem cells present in dental tissues. Notably, a previously unknown interaction of P. gingivalis bacteria with human stem cells that has impact on human immune response is discussed. In addition to this very specific interaction, the present review summarizes current knowledge regarding the immunomodulatory effect of P. gingivalis and other oral pathobionts, members of the oral microbiome, that pave the way for systemic and chronic diseases, thereby showing a link between periodontitis and rheumatoid arthritis.

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  • Tomoko Sumitomo, Yasushi Mori, Yuumi Nakamura, Mariko Honda-Ogawa, Seitaro Nakagawa, Masaya Yamaguchi, Hiroyuki Matsue, Yutaka Terao, Masanobu Nakata, Shigetada Kawabata .  Streptococcal cysteine protease-mediated cleavage of desmogleins is involved in the pathogenesis of cutaneous infection .  Frontiers in Cellular and Infection Microbiology8 ( 8 ) 10   2018Invited Reviewed

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    Streptococcus pyogenes is responsible for a wide variety of cutaneous infections ranging from superficial impetigo to fulminant invasive necrotizing fasciitis. Dysfunction of desmosomes is associated with the pathogenesis of cutaneous diseases. We identified streptococcal pyrogenic exotoxin B (SpeB) as a proteolytic factor that cleaves the extracellular domains of desmoglein 1 and 3. In an epicutaneous infection model, lesional skin infected with an speB deletion mutant were significantly smaller as compared to those caused by the wild-type strain. Furthermore, immunohistological analysis indicated cleavage of desmogleins that developed around the invasion site of the wild-type strain. In contrast, the speB mutant was preferentially found on the epidermis surface layer. Taken together, our findings provide evidence that SpeB-mediated degradation of desmosomes has a pathogenic role in development of S. pyogenes cutaneous infection.

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  • Chiaki Ota, Hirobumi Morisaki, Masanobu Nakata, Takafumi Arimoto, Haruka Fukamachi, Hideo Kataoka, Yoshiko Masuda, Noriyuki Suzuki, Takashi Miyazaki, Nobuo Okahashi, Hirotaka Kuwata .  Streptococcus sanguinis noncoding ciadependent small RNAs negatively regulate expression of type IV pilus retraction ATPase PilT and biofilm formation .  Infection and Immunity86 ( 3 ) e00894-17   2018Invited Reviewed

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    Small noncoding RNAs (sRNAs) have been identified as important regulators of gene expression in various cellular processes. cia-dependent small RNAs (csRNAs), a group of sRNAs that are controlled by the two-component regulatory system CiaRH, are widely conserved in streptococci, but their targets have been identified only in Streptococcus pneumoniae. Streptococcus sanguinis, a pioneer colonizer of teeth and one of the most predominant bacteria in the early oral biofilm, has been shown to have six csRNAs. Using computational target prediction and the luciferase reporter assay, we identified pilT, a constituent of the type IV pilus operon, as a negative regulatory target for one of the csRNAs, namely, csRNA1-1, in S. sanguinis. RNA-RNA electrophoretic mobility shift assay using a nucleotide exchange mutant of csRNA1-1 revealed that csRNA1-1 binds directly to pilT mRNA. In addition, csRNA1-1 and csRNA1-2, a putative gene duplication product of csRNA1-1 that is tandemly located in the S. sanguinis genome, negatively regulated S. sanguinis biofilm formation. These results suggest the involvement of csRNAs in the colonization step of S. sanguinis.

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  • Isenring Julia, Koehler Juliane, Nakata Masanobu, Frank Marcus, Jans Christoph, Renault Pierre, Danne Camille, Dramsi Shaynoor, Kreikemeyer Bernd, Oehmcke-Hecht Sonja .  Streptococcus gallolyticus subsp gallolyticus endocarditis isolate interferes with coagulation and activates the contact system .  VIRULENCE9 ( 1 ) 248 - 261   2018Invited Reviewed International coauthorship

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    DOI: 10.1080/21505594.2017.1393600

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  • 中田 匡宣, 川端 重忠 .  【改めて考えるレンサ球菌感染症】レンサ球菌の病原因子 .  化学療法の領域33 ( 6 ) 1183 - 1190   2017.5

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    化膿レンサ球菌(Streptococcus pyogenes),肺炎球菌(Streptococcus pneumoniae)およびB群レンサ球菌(Streptococcus agalactiae)は高い罹患率と死亡率をもたらす病原性レンサ球菌である。近年,抗菌薬耐性菌の増加により病原性レンサ球菌に対するワクチンの開発や改良が望まれている。菌体の定着やヒト免疫機構からの回避に寄与する病原因子群は感染成立と病態形成に必須であり,ワクチン抗原の候補となり得る。近縁種に共通して認められる病原因子も数多く存在し,レンサ球菌に普遍的な病原性を与えている。(著者抄録)

  • Nagase S, Matsue M, Mori Y, Honda-Ogawa M, Sugitani K, Sumitomo T, Nakata M, Kawabata S, Okamoto S. .  Comparison of antimicrobial spectrum and mechanisms of organic virgin coconut oil and lauric acid against bacteria. .  Journal of Wellness and Health Care41 ( 1 ) 87 - 95   2017Reviewed

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  • Ryuichi Sumioka, Masanobu Nakata, Nobuo Okahashi, Yixuan Li, Satoshi Wada, Masaya Yamaguchi, Tomoko Sumitomo, Mikako Hayashi, Shigetada Kawabata .  Streptococcus sanguinis induces neutrophil cell death by production of hydrogen peroxide .  PLOS ONE12 ( 2 ) e0172223   2017Invited Reviewed

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    Streptococcus is the dominant bacterial genus in the human oral cavity and a leading cause of infective endocarditis. Streptococcus sanguinis belongs to the mitis group of streptococci and produces hydrogen peroxide (H2O2) by the action of SpxB, a pyruvate oxidase. In this study, we investigated the involvement of SpxB in survival of S. sanguinis in human blood and whether bacterial H2O2 exhibits cytotoxicity against human neutrophils. Results of a bactericidal test with human whole blood revealed that the spxB mutation in S. sanguinis is detrimental to its survival in blood. When S. sanguinis strains were exposed to isolated neutrophils, the bacterial survival rate was significantly decreased by spxB deletion. Furthermore, human neutrophils exposed to the S. sanguinis wild-type strain, in contrast to those exposed to an spxB mutant strain, underwent cell death with chromatin de-condensation and release of web-like extracellular DNA, reflecting induction of neutrophil extracellular traps (NETs). Since reactive oxygen species-mediated NET induction requires citrullination of arginine residues in histone proteins and subsequent chromatin de-condensation, we examined citrullination levels of histone in infected neutrophils. It is important to note that the citrullinated histone H3 was readily detected in neutrophils infected with the wild-type strain, as compared to infection with the spxB mutant strain. Moreover, decomposition of streptococcal H2O2 with catalase reduced NET induction. These results suggest that H2O2 produced by S. sanguinis provokes cell death of neutrophils and NET formation, thus potentially affecting bacterial survival in the bloodstream.

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  • Mariko Honda-Ogawa, Tomoko Sumitomo, Yasushi Mori, Dalia Talat Hamd, Taiji Ogawa, Masaya Yamaguchi, Masanobu Nakata, Shigetada Kawabata .  Streptococcus pyogenes Endopeptidase O Contributes to Evasion from Complement-mediated Bacteriolysis via Binding to Human Complement Factor C1q .  JOURNAL OF BIOLOGICAL CHEMISTRY292 ( 10 ) 4244 - 4254   2017Invited Reviewed

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    Streptococcus pyogenes secretes various virulence factors for evasion from complement-mediated bacteriolysis. However, full understanding of the molecules possessed by this organism that interact with complement C1q, an initiator of the classical complement pathway, remains elusive. In this study, we identified an endopeptidase of S. pyogenes, PepO, as an interacting molecule, and investigated its effects on complement immunity and pathogenesis. Enzyme-linked immunosorbent assay and surface plasmon resonance analysis findings revealed that S. pyogenes recombinant PepO bound to human C1q in a con-centration-dependent manner under physiological conditions. Sites of inflammation are known to have decreased pH levels, thus the effects of PepO on bacterial evasion from complement immunity was analyzed in a low pH condition. Notably, under low pH conditions, PepO exhibited a higher affinity for C1q as compared with IgG, and PepO inhibited the binding of IgG to C1q. In addition, pepO deletion rendered S. pyogenes more susceptible to the bacteriocidal activity of human serum. Also, observations of the morphological features of the pepO mutant strain (Delta pepO) showed damaged irregular surfaces as compared with the wild-type strain (WT). WT-infected tissues exhibited greater severity and lower complement activity as compared with those infected by Delta pepO in a mouse skin infection model. Furthermore, WT infection resulted in a larger accumulation of C1q than that with Delta pepO. Our results suggest that interaction of S. pyogenes PepO with C1q interferes with the complement pathway, which enables S. pyogenes to evade complement-mediated bacteriolysis under acidic conditions, such as seen in inflammatory sites.

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  • Masaya Yamaguchi, Masanobu Nakata, Ryuichi Sumioka, Yujiro Hirose, Satoshi Wada, Yukihiro Akeda, Tomoko Sumitomo, Shigetada Kawabata .  Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems .  VIRULENCE8 ( 8 ) 1516 - 1524   2017Invited Reviewed

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    Streptococcus pneumoniae is a leading cause of bacterial meningitis. Here, we investigated whether pneumococcal paralogous zinc metalloproteases contribute to meningitis onset. Findings of codonbased phylogenetic analyses indicated 3 major clusters in the Zmp family; ZmpA, ZmpC, and ZmpB, with ZmpD as a subgroup. In vitro invasion assays of human brain microvascular endothelial cells (hBMECs) showed that deletion of the zmpC gene in S. pneumoniae strain TIGR4 significantly increased bacterial invasion into hBMECs, whereas deletion of either zmpA or zmpB had no effect. In a mouse meningitis model, the zmpC deletion mutant exhibited increased invasion of the brain and was associated with increased matrix metalloproteinase-9 in plasma and mortality as compared with the wild type. We concluded that ZmpC suppresses pneumococcal virulence by inhibiting bacterial invasion of the central nervous system. Furthermore, ZmpC illustrates the evolutional theory stating that gene duplication leads to acquisition of novel function to suppress excessive mortality.

    DOI: 10.1080/21505594.2017.1328333

    Web of Science

    PubMed

  • Okahashi N, Nakata M, Kuwata H, Kawabata S. .  Streptococcus oralis induces lysosomal impairment of macrophages via bacterial hydrogen peroxide. .  Infection and Immunity84 ( 7 ) 2042 - 2050   2016Reviewed

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    DOI: 10.1128/IAI.00134-16

  • Yamaguchi M, Hirose Y, Nakata M, Uchiyama S, Yamaguchi Y, Goto K, Sumitomo T, Lewis A, Kawabata S. .  Evolutionary inactivation of a sialidase in group B Streptococcus. .  Scientific Reports6   28852   2016Reviewed

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    DOI: 10.1038/srep28852

  • Sumitomo T, Nakata M, Higashino M, Yamaguchi M, and Kawabata S. .  Group A Streptococcus exploits human plasminogen for bacterial translocation across epithelial barrier via tricellular tight junctions. .  Scientific Reports6   20069   2016Reviewed

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    DOI: 10.1038/srep20069

  • Morita C, Sumioka R, Nakata M, Okahashi N, Wada S, Yamashiro T, Hayashi M, Hamada S, Sumitomo T, Kawabata S. .  Cell wall-anchored nuclease of Streptococcus sanguinis contributes to escape from neutrophil extracellular trap-mediated bacteriocidal activity. .  PLoS One9 ( 8 ) e103125   2014Reviewed

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    DOI: 10.1371/journal.pone.0103125

  • Okahashi N, Sumitomo T, Nakata M, Sakurai A, Kuwata H, Kawabata S. .  Hydrogen peroxide contributes to the epithelial cell death induced by the oral mitis group of streptococci. .  PLoS One9 ( 1 ) e88136   2014Reviewed

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    DOI: 10.1371/journal.pone.0088136

  • Honda-Ogawa M, Ogawa T, Terao Y, Sumitomo T, Nakata M, Ikebe K, Maeda Y, Kawabata S. .  Cysteine proteinase from Streptococcus pyogenes enables evasion of innate immunity via degradation of complement factors. .  Journal of Biological Chemistry288 ( 22 ) 15854 - 15864   2013Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M113.469106

  • Okahashi N, Nakata M, Sumitomo T, Terao Y, Kawabata S. .  Hydrogen peroxide produced by oral streptococci induces macrophage cell death. .  PLoS One8 ( 5 ) e62563   2013Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1371/journal.pone.0062563

  • Sumitomo T, Nakata M, Higashino M, Terao Y, Kawabata S. .  Group A streptococcal cysteine protease cleaves epithelial junctions and contributes to bacterial translocation. .  Journal of Biological Chemistry288 ( 19 ) 13317 - 13324   2013Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M113.459875

  • 中田 匡宣, 川端 重忠 .  【細菌の病原遺伝子の発現調節機構】病原性レンサ球菌の二成分制御系シグナル伝達機構 .  化学療法の領域29 ( 1 ) 42 - 50   2012.12

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    Language:Japanese   Publisher:(株)医薬ジャーナル社  

    病原性レンサ球菌は十数対の二成分制御系を巧みにあやつり、感染部位における環境の感知と遺伝子の発現調節を行う。細菌性肺炎のおもな起因菌である肺炎球菌では多数の二成分制御系が病原性に関与している。それぞれの二成分制御系により発現調節される病原因子群も徐々に明らかになってきており、病原性につながる複雑なシグナル伝達経路が予想される。一方、咽頭炎や膿痂疹を惹起するA群レンサ球菌(溶血性レンサ球菌)でも病原性に関与する複数の二成分制御系が明らかになっている。A群レンサ球菌は、ときとして全身感染をともなう劇症化を惹き起こす。劇症化にかかわる要因のひとつとして特定の二成分制御系の変異が注目されている。(著者抄録)

  • Kimura KR, Nakata M, Sumitomo T, Kreikemeyer B, Podbielski A, Terao Y, Kawabata S. .  Involvement of T6 pili in biofilm formation by serotype M6 Streptococcus pyogenes. .  Journal of Bacteriology194 ( 4 ) 804 - 812   2012Reviewed

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    DOI: 10.1128/JB.06283-11

  • Sumitomo T, Nakata M, Yamaguchi M, Terao Y, Kawabata S. .  S-carboxymethylcysteine inhibits adherence of Streptococcus pneumoniae to human alveolar epithelial cells. .  Journal of Medical Microbiology61 ( Pt1 ) 101 - 108   2012Reviewed

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    DOI: 10.1099/jmm.0.033688-0

  • Nakata M, Kimura KR, Sumitomo T, Wada S, Sugauchi A, Oiki E, Higashino M, Kreikemeyer B, Podbielski A, Okahashi N, Hamada S, Isoda R, Terao Y, Kawabata S. .  Assembly mechanism of FCT region type 1 pili in serotype M6 Streptococcus pyogenes. .  Journal of Biological Chemistry286 ( 43 ) 37566 - 37577   2011Reviewed

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    DOI: 10.1074/jbc.M111.239780

  • Sumitomo T, Nakata M, Higashino M, Jin Y, Terao Y, Fujinaga Y, Kawabata S. .  Streptolysin S contributes to group A streptococcal translocation across an epithelial barrier. .  Journal of Biological Chemistry286 ( 4 ) 2750 - 2761   2011Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M110.171504

  • Okahashi N, Nakata M, Terao Y, Isoda R, Sakurai A, Sumitomo T, Yamaguchi M, Kimura RK, Oiki E, Kawabata S, Ooshima T. .  Pili of oral Streptococcus sanguinis bind to salivary amylase and promote the biofilm formation. .  Microbial Pathogenesis50 ( 3-4 ) 148 - 154   2011Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.micpath.2011.01.005

  • Okahashi N, Okinaga T, Sakurai A, Terao Y, Nakata M, Nakashima K, Shintani S, Kawabata S, Ooshima T, Nishihara T. .  Streptococcus sanguinis induces foam cell formation and cell death of macrophages in association with production of reactive oxygen species. .  FEMS Microbiology Letters323 ( 2 ) 164 - 170   2011Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1574-6968.2011.02375.x

  • Okahashi N, Nakata M, Sakurai A, Terao Y, Hoshino T, Yamaguchi M, Isoda R, Sumitomo T, Nakano K, Kawabata S, Ooshima T. .  Pili of oral Streptococcus sanguinis bind to fibronectin and contribute to cell adhesion. .  Biochemical and Biophysical Research Communications391 ( 2 ) 1192 - 1196   2010Reviewed

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    DOI: 10.1016/j.bbrc.2009.12.029

  • Nakata M, Köller T, Moritz K, Ribardo D, Jonas L, McIver KS, Sumitomo T, Terao Y, Kawabata S, Podbielski A, Kreikemeyer B. .  Mode of expression and functional characterization of FCT-3 pilus region encoded proteins in the Streptococcus pyogenes serotype M49. .  Infection and Immunity77 ( 1 ) 32 - 44   2009Reviewed

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/IAI.00772-08

  • Panchaud A, Guy L, Collyn F, Haenni M, Nakata M, Podbielski A, Moreillon P, Roten CA. .  M-protein and other intrinsic virulence factors of Streptococcus pyogenes are encoded on an ancient pathogenicity island. .  BMC Genomics10   198   2009Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1186/1471-2164-10-198

  • Köller T, Nelson D, Nakata M, Kreutzer M, Fischetti VA, Glocker MO, Podbielski A, Kreikemeyer B. .  PlyC, a novel bacteriophage lysin for compartment-dependent proteomics of group A streptococci. .  Proteomics8 ( 1 ) 140 - 148   2008Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/pmic.200700001

  • 中田 匡宣, 寺尾 豊, 川端 重忠 .  【口腔での免疫 最近の進歩と疾患】レンサ球菌感染症に対する免疫療法の可能性 .  炎症と免疫15 ( 6 ) 701 - 706   2007.10

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    Language:Japanese   Publisher:(株)先端医学社  

    病原性レンサ球菌は、ヒトに対してさまざまな疾患を起こすことが知られている。おもに飛沫によって伝播し、口腔やその周辺組織などに定着する。レンサ球菌感染症の予防法として、免疫療法-ワクチン-の開発が精力的に試みられている。う蝕原性細菌であるStreptococcus mutansに対しては、表層蛋白抗原PAcの受動免疫による免疫療法の研究などが進められている。上気道感染症を惹起するStreptococcus pyogenesに対しては、病因論に基づいた抗付着因子ワクチンや多価ワクチンの検索が行われている。肺炎の起因菌の1つであるStreptococcus pneumoniaeに対しては、現行の抗莢膜多糖ワクチンの改変だけでなく、新たな蛋白性ワクチンの開発も試みられている。将来的には、これらを統合するような研究から、口腔フローラ全体をコントロールしうる免疫療法の確立が期待される。(著者抄録)

  • Klenk M, Nakata M, Podbielski A, Skupin B, Schroten H, Kreikemeyer B. .  Streptococcus pyogenes serotype-dependent and independent changes in infected HEp-2 epithelial cells. .  ISME Journal1 ( 8 ) 678 - 692   2007Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/ismej.2007.54

  • Kreikemeyer B, Nakata M, Köller T, Hildisch H, Kourakos V, Standar K, Kawabata S, Glocker MO, Podbielski A. .  The Streptococcus pyogenes serotype M49 Nra-Ralp3 transcriptional regulatory network and its control on virulence factor expression from the novel ERES pathogenicity region. .  Infection and Immunity75 ( 12 ) 5698 - 5710   2007Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1128/IAI.00175-07

  • Klenk M, Koczan D, Guthke R, Nakata M, Thiesen HJ, Podbielski A, Kreikemeyer B. .  Global epithelial cell transcriptional responses reveal Streptococcus pyogenes Fas regulator activity association with bacterial aggressiveness. .  Cellular Microbiology7 ( 9 ) 1237 - 1250   2005Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1462-5822.2005.00548.x

  • Kreikemeyer B, Nakata M, Oehmcke S, Gschwendtner C, Normann J, Podbielski A. .  Streptococcus pyogenes collagen type I-binding Cpa surface protein. Expression profile, binding characteristics, biological functions, and potential clinical impact. .  Journal of Biological Chemistry280 ( 39 ) 33228 - 33239   2005Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M502896200

  • Nakata M, Podbielski A, Kreikemeyer B. .  MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin-mediated translocation system genes. .  Molecular Microbiology57 ( 3 ) 786 - 803   2005Reviewed

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1365-2958.2005.04730.x

  • Nakagawa I, Amano A, Mizushima N, Yamamoto A, Yamaguchi H, Kamimoto T, Nara A, Funao J, Nakata M, Tsuda K, Hamada S, Yoshimori T. .  Autophagy defends cells against invading group A Streptococcus. .  Science306 ( 5698 ) 1037 - 1040   2004Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1126/science.1103966

  • Nakagawa I, Nakata M, Kawabata S, Hamada S. .  Transcriptome analysis and gene expression profiles of early apoptosis-related genes in Streptococcus pyogenes-infected epithelial cells. .  Cellular Microbiology6 ( 10 ) 939 - 952   2004Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1462-5822.2004.00412.x

  • Kreikemeyer B, Oehmcke S, Nakata M, Hoffrogge R, Podbielski A. .  Streptococcus pyogenes fibronectin-binding protein F2: expression profile, binding characteristics, and impact on eukaryotic cell interactions. .  Journal of Biological Chemistry279 ( 16 ) 15850 - 15859   2004Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M313613200

  • Nakagawa I, Kurokawa K, Yamashita A, Nakata M, Tomiyasu Y, Okahashi N, Kawabata S, Yamazaki K, Shiba T, Yasunaga T, Hayashi H, Hattori M, Hamada S. .  Genome sequence of an M3 strain of Streptococcus pyogenes reveals a large-scale genomic rearrangement in invasive strains and new insights into phage evolution. .  Genome Research13 ( 6A ) 1042 - 1055   2003Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1101/gr.1096703

  • Terao Y, Kawabata S, Nakata M, Nakagawa I, Hamada S. .  Molecular characterization of a novel fibronectin-binding protein of Streptococcus pyogenes strains isolated from toxic shock-like syndrome patients. .  Journal of Biological Chemistry277 ( 49 ) 47428 - 47435   2002Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M209133200

  • Nakagawa I, Nakata M, Yamamura T, Wakisaka S, Kawabata S, Hamada S. .  Infection and pathogenesis of a murine strain of Escherichia coli with genetically introduced Shiga toxin type I operon in conventional mice. .  Microbial Pathogenesis33 ( 2 ) 63 - 72   2002Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1006/mpat.2002.0518

  • Nakagawa I, Nakata M, Kawabata S, Hamada S. .  Cytochrome c-mediated caspase-9 activation triggers apoptosis in Streptococcus pyogenes-infected epithelial cells .  Cellular Microbiology3 ( 6 ) 395 - 405   2001Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1046/j.1462-5822.2001.00122.x

  • Nakagawa I, Nakata M, Kawabata S, Hamada S. .  Regulated expression of the Shiga toxin B gene induces apoptosis in mammalian fibroblastic cells. .  Molecular Microbiology33 ( 6 ) 1190 - 1199   1999Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1046/j.1365-2958.1999.01564.x

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Books

  • Group A Streptococcus: Methods and Protocols

    Nakata M, Kawabata S.( Role: Joint author ,  Detection of fibronectin-binding proteins of Streptococcus pyogenes by ligand-blot analysis.)

    Springer Nature  2020 

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    Total pages:10   Responsible for pages:181-190   Language:English Book type:Scholarly book

  • 口腔微生物学・免疫学 第5版 Reviewed

    中田匡宣( Role: Joint author ,  微生物の遺伝学,微生物遺伝子の変化,微生物遺伝子の応用)

    医歯薬出版株式会社  2021.12 

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    Total pages:17   Language:Japanese

  • 口腔微生物学・免疫学 第4版

    中田匡宣,川端重忠 他( Role: Joint author ,  微生物の遺伝学,微生物遺伝子の変化,微生物遺伝子の応用)

    医歯薬出版株式会社  2016 

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    Total pages:17   Responsible for pages:32〜48   Language:Japanese Book type:Scholarly book

  • 病原性レンサ球菌の病原因子の機能解析.

    寺尾豊, 中田匡宣, 住友倫子, 磯田竜太朗, 川端重忠( Role: Joint author)

    大阪大学出版会  2008.3 

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    Book type:General book, introductory book for general audience

  • 生命歯科医学のカッティング・エッジ

    寺尾豊,住友倫子,中田匡宣,磯田竜太朗,川端重忠 他( Role: Contributor)

    大阪大学出版会  2008 

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    Total pages:11   Responsible for pages:68〜78   Language:Japanese Book type:Scholarly book

  • The 9th International Conference on Shallow-Level Centers in Semiconductors : proceedings of the Yamada Conference LIV, held in Awaji island, Hyogo, Japan, 24-27 September 2000

    International Conference on Shallow-Level Centers in Semiconductors

    Elsevier Science  2001 

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    Language:English

    CiNii Research

  • Streptococci and Streptococcal Diseases edited by Martin DR, and Tagg JR.Effects of receptor-globulins on invasive group A streptococcal infection.

    Nakagawa I, Kimura RK, Nakata M, Kuwata H, Kawabata S, Hamada S( Role: Joint author)

    Securacopy Press  2000.10 

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    Book type:Scholarly book

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MISC

  • 口唇炎連鎖球菌 ヒトの口腔のサイレントマジョリティー(Oral mitis group streptococci: A silent majority in our oral cavity)

    Okahashi Nobuo, Nakata Masanobu, Kuwata Hirotaka, Kawabata Shigetada

    Microbiology and Immunology   66 ( 12 )   539 - 551   2022.12

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    Language:English   Publisher:John Wiley & Sons Australia, Ltd  

  • 化膿レンサ球菌による温度感受性の翻訳制御

    中田 匡宣

    南九州歯学会雑誌   3 ( 1 )   1 - 7   2022.9

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    Language:Japanese   Publisher:南九州歯学会  

    化膿レンサ球菌(Streptococcus pyogenes)は主に上気道や皮膚に限局性の化膿性疾患を惹き起こす。また,免疫性続発症や劇症型溶血性レンサ球菌感染症の原因になる。化膿レンサ球菌が宿主に定着し,多様な疾患を惹き起こすためには,環境条件に応じて分泌タンパク質の発現を調節する必要がある。化膿レンサ球菌の線毛は宿主組織への付着因子であるとともに,バイオフィルム形成や宿主免疫の回避に寄与することが報告されている。また、線毛のメジャーサブユニットの抗原性はTタイピングに用いられてきた。本稿では,化膿レンサ球菌の特定のサブセットから温度依存性に線毛が産生される機構を紹介する。この現象は,線毛遺伝子に対する転写因子であるNraの温度に依存する転写後翻訳制御に起因する。すなわち,nra mRNAの翻訳領域に位置する推定ステムループ構造がサーモセンサーとして機能し,温度感受性にnra mRNAの翻訳と線毛の産生を誘導する。この現象の発見により,化膿レンサ球菌の組織指向性と線毛発現様式の関連とともに,mRNAによる温度感知と翻訳制御が化膿レンサ球菌の宿主環境への適応に重要であることが示唆された。(著者抄録)

  • Secondary streptococcal infection following influenza(タイトル和訳中)

    Okahashi Nobuo, Sumitomo Tomoko, Nakata Masanobu, Kawabata Shigetada

    Microbiology and Immunology   66 ( 6 )   253 - 263   2022.6

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    Language:English   Publisher:John Wiley & Sons Australia, Ltd  

  • Small regulatory RNAs of oral streptococci and periodontal bacteria(タイトル和訳中)

    Oogai Yuichi, Nakata Masanobu

    The Japanese Dental Science Review   57   209 - 216   2021.11

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    Language:English   Publisher:日本歯科医学会  

  • Genetics, Structure, and Function of Group A Streptococcal Pili Reviewed

    Nakata, M., Kreikemeyer, B.

    Frontiers in Microbiology   2021

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • Structural analysis of Streptococcus pyogenes hyaluronidase and in silico analysis based on structural models

    東孝太郎, 東孝太郎, 山口雅也, 中田匡宣, 武部克希, 住友倫子, 鈴木守, 川端重忠

    Journal of Oral Biosciences Supplement (Web)   2021   2021

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  • Investigation of factors contributing to the invasiveness of Streptococcus pyogenes emm 89

    広瀬雄二郎, 山口雅也, 秋山徹, 竹本訓彦, 奥野ルミ, 山口貴弘, 大塚仁, 住友倫子, 中田匡宣, 川端重忠

    日本細菌学雑誌(Web)   75 ( 1 )   2020

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  • 化膿レンサ球菌におけるヒアルロン酸分解酵素の分子系統解析および結晶構造解析

    東孝太郎, 東孝太郎, 山口雅也, 中田匡宣, 中田匡宣, 武部克希, 住友倫子, 鈴木守, 川端重忠

    日本分子生物学会年会プログラム・要旨集(Web)   43rd   2020

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  • Oral biofilms from symbiotic to pathogenic interactions and associated disease – Connection of Periodontitis and Rheumatic arthritis by peptidylarginine deiminase. Reviewed

    Kriebel K, Hieke C, Müller-Hilke B, Nakata M, Kreikemeyer B.

    Frontiers in Microbiology   2018

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • Streptococcus sanguinisが産生するSrtCのX線結晶構造

    武部克希, 中田匡宣, 川端重忠, 鈴木守

    日本結晶学会年会講演要旨集   2018   2018

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  • 化膿レンサ球菌におけるヒアルロン酸分解酵素の分子系統解析およびタンパク質構造解析

    東孝太郎, 武部克希, 山口雅也, 住友倫子, 中田匡宣, 鈴木守, 川端重忠

    Journal of Oral Biosciences Supplement (Web)   2018   2018

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  • Group A Streptococcus exploits human plasminogen for bacterial translocation across epithelial barrier via tricellular tight junctions

    Tomoko Sumitomo, Masanobu Nakata, Miharu Higashino, Masaya Yamaguchi, Shigetada Kawabata

    SCIENTIFIC REPORTS   7   46388   2017.6

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    Publisher:NATURE PUBLISHING GROUP  

    DOI: 10.1038/srep46388

    Web of Science

    PubMed

  • 【改めて考えるレンサ球菌感染症】レンサ球菌の病原因子

    中田 匡宣, 川端 重忠

    化学療法の領域   33 ( 6 )   1183 - 1190   2017.5

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    Language:Japanese   Publisher:(株)医薬ジャーナル社  

    化膿レンサ球菌(Streptococcus pyogenes),肺炎球菌(Streptococcus pneumoniae)およびB群レンサ球菌(Streptococcus agalactiae)は高い罹患率と死亡率をもたらす病原性レンサ球菌である。近年,抗菌薬耐性菌の増加により病原性レンサ球菌に対するワクチンの開発や改良が望まれている。菌体の定着やヒト免疫機構からの回避に寄与する病原因子群は感染成立と病態形成に必須であり,ワクチン抗原の候補となり得る。近縁種に共通して認められる病原因子も数多く存在し,レンサ球菌に普遍的な病原性を与えている。(著者抄録)

  • 【改めて考えるレンサ球菌感染症】レンサ球菌の病原因子

    中田 匡宣, 川端 重忠

    化学療法の領域   33 ( 6 )   1183 - 1190   2017.5

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    化膿レンサ球菌(Streptococcus pyogenes),肺炎球菌(Streptococcus pneumoniae)およびB群レンサ球菌(Streptococcus agalactiae)は高い罹患率と死亡率をもたらす病原性レンサ球菌である。近年,抗菌薬耐性菌の増加により病原性レンサ球菌に対するワクチンの開発や改良が望まれている。菌体の定着やヒト免疫機構からの回避に寄与する病原因子群は感染成立と病態形成に必須であり,ワクチン抗原の候補となり得る。近縁種に共通して認められる病原因子も数多く存在し,レンサ球菌に普遍的な病原性を与えている。(著者抄録)

  • レンサ球菌感染症に対する免疫療法の可能性.

    中田匡宣, 川端重忠.

    化学療法の領域   2017

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  • M3型化膿レンサ球菌が産生する線毛タンパク質FctA3の結晶構造解析

    寒川剛, 武部克希, 中田匡宣, 川端重忠, 鈴木守

    日本結晶学会年会講演要旨集   2016   2016

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  • 内の目・外の目(第155回) 肺炎球菌と現行ワクチン

    中田 匡宣, 川端 重忠

    日本歯科医師会雑誌   68 ( 4 )   294 - 295   2015.7

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  • 肺炎球菌と現行ワクチン.

    中田匡宣, 川端重忠.

    日本歯科医師会雑誌   2015

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  • 病原性レンサ球菌の二成分制御系シグナル伝達機構.

    中田匡宣, 川端重忠.

    化学療法の領域   2013

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  • 口腔内微生物の網羅的検出

    中田 匡宣, 川端 重忠

    歯界展望   116 ( 4 )   748 - 749   2010.10

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    Language:Japanese   Publisher:医歯薬出版(株)  

  • 口腔内微生物の網羅的検出.

    中田匡宣, 川端重忠.

    歯界展望   2010

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  • A群レンサ球菌の病原性発現に関する分子機構

    川端 重忠, 寺尾 豊, 中田 匡宣

    感染・炎症・免疫   38 ( 1 )   2 - 13   2008.3

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    A群レンサ球菌(GAS;Group A streptococci)は多彩な病原因子を駆使し、ヒトに対してさまざまな疾患を引き起こす。なかでも侵襲性および劇症型GAS感染症は、再興感染症として注目を集め、世界的には年間十数万人にものぼる死亡例が報告されている。しかしながら、GASが有する病原因子の多様性から劇症型GAS感染症や二次性疾患の予防法は確立されていない。21世紀に入り、GASの全ゲノム解析が急速に進み、新たな知見が蓄積されつつある。ゲノムならびにプロテオーム解析から、GASの組織への付着・侵入と組織内増殖等に関与する新規の病原因子が数多く見い出されてきた。本稿では、感染の各段階におけるGASの病原性発現機構を中心に概説する。また、GASの重症化に関与すると推察される宿主因子や、今後期待される研究展開についても紹介する。(著者抄録)

  • A群レンサ球菌の病原性発現に関する分子機構.

    中田匡宣, 寺尾豊,川端重忠.

    感染・炎症・免疫   2008

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  • A群レンサ球菌 Pilus 発現機構の解析

    中田 匡宣, 川端 重忠

    日本細菌学雑誌   62 ( 1 )   83 - 83   2007.2

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    CiNii Research

  • レンサ球菌感染症に対する免疫療法の可能性.

    中田匡宣,寺尾豊,川端重忠.

    炎症と免疫   2007

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▼display all

Presentations

  • Higashi K, Yamaguchi M, Takebe K, Nakata M, Sumitomo T, Suzuki M, Varki A, Nizet V, Kawabata S.   Hyaluronidase in Streptococcus pyogenes – analysis based on structural biology and molecular phylogenetics.   International coauthorship International conference

    Society for Glycobiology 2023 Annal meeting  2023.11 

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    Event date: 2023.11

  • 田中 友三佳,大貝 悠一,松本 愛理,中田 匡宣.   Fusobacterium nucleatumが Fap2を介してAggregatibacter actinomycetemcomitansと共凝集する機構の解析.  

    第65回歯科基礎医学会学術大会  2023.9 

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    Event date: 2023.9

  • 中田 匡宣,窪田 星子,広瀬 雄二郎,山口 雅也,住友倫子,川端重忠.   化膿レンサ球菌のRNase Yによる線毛産生量の調節.  

    第65回歯科基礎医学会学術大会  2023.9 

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    Event date: 2023.9

    Language:Japanese  

  • 武部 克希,鈴木 守,東 孝太郎,山口 雅也,住友 倫子,川端 重忠,中田 匡宣.   Streptococcus sanguinis が産生する線毛タンパク質の X線結晶構造解析.  

    第65回 歯科基礎医学会学術大会  2023.9 

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    Event date: 2023.9

  • 松本愛理,大貝悠一,田端厚之,住友倫子,中田匡宣.   ミティス群レンサ球菌が産生する細胞外小胞の作用特性の解明.  

    九州微生物研究フォーラム2023  2023.9 

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    Event date: 2023.9

  • 赤松 由佳子, 住友倫子, 高原悠樹, 広瀬雄二郎, 山口雅也, 中田匡宣, 秋山茂久, 明石満, 川端重忠.   交互積層細胞コーティング法を用いた三次元肺組織モデルの構築と感染モデルへの応用.  

    第75回 日本細菌学会関西支部総会  2022.11 

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    Event date: 2022.11

  • 赤松 由佳子, 住友 倫子, 高原 悠樹, 山口 雅也, 中田 匡宣, 明石 満, 川端 重忠.   肺炎球菌を感染させた三次元肺組織モデルにおける上皮バリアの機能障害と炎症応答の解析.  

    第64回 歯科基礎医学会学術大会  2022.9 

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    Event date: 2022.9

    Venue:徳島市  

  • 高原 悠樹, 住友 倫子, 河野 正充, 赤松 由佳子, 山口 雅也, 中田 匡宣, 保富 宗城, 川端 重忠.   肺炎球菌のニューモライシン依存的な鼻粘膜上皮バリア傷害と脳伝播機構の解析.  

    第52回 レンサ球菌研究会  2022.7 

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    Event date: 2022.7

  • 高原悠樹,住友倫子,河野正充,山口雅也,中田匡宣,保富宗城,川端重忠.   肺炎球菌のニューモライシンによる鼻粘膜上皮バリアの傷害と脳伝播機構の解析  

    第95回日本細菌学会総会  2022.3 

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    Event date: 2022.3

  • Nasal epithelial barrier dysfunction involved in non-hematogenous pneumococcal dissemination to brain tissue   International conference

    2021.12 

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    Event date: 2021.12

    Language:English  

  • 高原悠樹, 住友倫子, 山口雅也, 中田匡宣, 川端重忠   肺炎球菌のニューモライシン依存的な鼻粘膜バリア傷害と脳への伝播機構の関連  

    第63回歯科基礎医学会学術大会  2021.10 

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    Event date: 2021.10

  • 中田匡宣   化膿レンサ球菌におけるサーモセンサーの発見   Invited

    第3回南九州歯学会学術大会  2021  第3回南九州歯学会学術大会

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    Event date: 2021.9

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  • 大貝悠一, 藤田愛弓, 中田匡宣, 小松澤均   Aggregatibacter actinomycetemcomitansは血清培養時に共凝集性を促進する.  

    第94回 日本細菌学会総会  2021.3 

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    Event date: 2021.3

  • 中田匡宣   Thermosensitive pilus production by Streptococcus pyogenes via mRNA thermosensor.   Invited

    第93回 日本細菌学会総会 

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    Event date: 2020.2

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  • 中田匡宣, 住友倫子, 川端重忠.   温度感受性転写因子の翻訳効率に依存する化膿レンサ球菌の線毛発現.  

    第61回 歯科基礎医学会学術大会 

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    Event date: 2019.10

    Language:Japanese   Presentation type:Poster presentation  

  • Sumitomo T, Hamd DT, Honda-Ogawa M, Mori Y, Yamaguchi M, Nakata M, Kawabata S.   Two-component regulatory system TCS08 contributes to pathogenesis in pneumococcal pneumonia.   International conference

    ASM Microbe 2019 

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    Event date: 2019.6

    Language:English   Presentation type:Poster presentation  

  • 中田匡宣, 住友倫子, 川端重忠.   化膿レンサ球菌による温度依存性の線毛産生.  

    第92回 日本細菌学会総会 

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    Event date: 2019.4

    Language:Japanese   Presentation type:Poster presentation  

  • Yamaguchi M, Goto K, Hirose Y, Yamaguchi Y, Sumitomo T, Nakata M, Kawabata S.   Identification of novel pneumococcal virulence factor CbpJ by molecular evolutional analysis.   International conference

    Gordon Research Conference 

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    Event date: 2018.8

    Language:English   Presentation type:Oral presentation (general)  

  • Hirose Y, Yamaguchi M, Goto K, Sumitomo T, Nakata M, Kawabata S.   Pneumococcal Ccs4 facilitates its invasion into brain tissue and develops meningitis.   International conference

    118th General Meeting of American Society for Microbiology 

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    Event date: 2018.6

    Language:English   Presentation type:Poster presentation  

  • Yamaguchi M, Hirose Y, GotoK, Sumitomo T, Nakata M, Kawabata S.   Streptococcus pneumoniae evades host innate immunity through parallel β-helix protein PfbA.   International conference

    20th Lancefield International Symposium on Streptococci and Streptococal Disease. 

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    Event date: 2017.10

    Language:English   Presentation type:Poster presentation  

  • 中田匡宣, 住友倫子, 川端重忠.   化膿レンサ球菌における温度感受性の線毛発現機構.  

    第59回 歯科基礎医学会学術大会 

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    Event date: 2017.9

    Language:Japanese   Presentation type:Oral presentation (general)  

  • Sumitomo T, Mori Y, Nakamura Y, Honda-Ogawa M, Yamaguchi M, Terao Y, Nakata M, Kawabata S.   Streptococcal cysteine protease-mediated cleavage of desmogleins contributes to development of cutaneous infection.   International conference

    IUMS2017 

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    Event date: 2017.7

    Language:English   Presentation type:Poster presentation  

  • 中田匡宣, 住友倫子, 山口雅也, 川端重忠.   化膿レンサ球菌の線毛発現機構.  

    第37回 近畿腸管微生物研究会 

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    Event date: 2017.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  • Honda M, Sumitomo T, Mori Y, Yamaguchi M, Nakata M, Kawabata S.   Involvement of Group A streptococcal endopeptidase O in evasion from complement-mediated bacteriolysis via binding to complement C1q.   International conference

    13th Korea-Japan International Symposium on Microbiology 

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    Event date: 2016.5

    Language:English   Presentation type:Poster presentation  

  • 中田匡宣,住友倫子,山口雅也,川端重忠.   培養温度の変化が肺炎球菌の血中での生存に及ぼす影響.  

    第89回 日本細菌学会総会 

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    Event date: 2016.3

    Language:Japanese   Presentation type:Poster presentation  

  • Sumitomo T, Nakata M, Yamaguchi M, Kawabata S.   Group A Streptococcus penetrates across an epithelial barrier via tricellular tight junctions.   International conference

    115th General Meeting of American Society for Microbiology 

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    Event date: 2015.5 - 2015.6

    Language:English   Presentation type:Poster presentation  

  • 中田匡宣,住友倫子,寺尾豊,川端重忠.   Transcriptional regulation of FCT type 1 pili in serotype M6 Streptococcus pyogenes.  

    第88回日本細菌学会総会 

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    Event date: 2015.3

    Language:Japanese   Presentation type:Poster presentation  

  • Yamaguchi M, Yamaguchi Y, Nakata M, Henningham A, Olson J, Dahesh S, Cole J, Kawabata S, Varki A, Nizet V.   Enzymatically active extracellular hyaluronidase (HylA) of group A Streptococcus promotes intracellular survival and virulence.   International conference

    SFG and JSCR2014 Joint Annual Meeting 

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    Event date: 2014.11

    Language:English   Presentation type:Poster presentation  

  • Morita C, Nakata M, Sumioka R, Okahashi N, Hamada S, Sumitomo T, Kawabata S.   Role of Streptococcus sanguinis cell wall-anchored nuclease.   International conference

    19th Lancefield International Symposium on Streptococci and Streptococal Disease 

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    Event date: 2014.11

    Language:English   Presentation type:Poster presentation  

  • 中田匡宣,住友倫子,川端重忠.   Streptococcus sanguinisが産生する菌体表層ヌクレアーゼの解析.  

    第34回 近畿腸管微生物研究会 

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    Event date: 2014.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  • 中田匡宣,住友倫子,浜田茂幸,川端重忠.   Regulation of pilus gene expression in FCT type 3 strain of Streptococcus pyogenes.  

    第87回 日本細菌学会総会 

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    Event date: 2014.3

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

  • Nakata M, Kawabata S.   Mode of expression and assembly mechanism of Group A Streptococcal pili.   Invited International conference

    12th Awaji International Forum on Infection and Immunity 

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    Event date: 2013.9

    Language:English   Presentation type:Oral presentation (invited, special)  

  • Sumitomo T, Nakata M, Higashino M, Terao Y, Kawabata S.   Group A streptococcal pyrogenic exotoxin B cleaves epithelial junctions and contributes to bacterial translocation.  

    113th General Meeting of American Society for Microbiology 

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    Event date: 2013.5

    Language:English   Presentation type:Poster presentation  

  • Nakata M, Sumitomo T, Kawabata S.   Assembly mechanism of T6 pili and its involvement in biofilm formation.   International conference

    GAS Infections 2013 

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    Event date: 2013.3

    Language:English   Presentation type:Symposium, workshop panel (public)  

  • 中田匡宣,住友倫子,寺尾豊,浜田茂幸,川端重忠.   Cell wall anchoring mechanism of FCT region type 3 pili in Streptococcus pyogenes.  

    第86回 日本細菌学会総会 

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    Event date: 2013.3

    Language:Japanese   Presentation type:Poster presentation  

  • Sumitomo T, Nakata M, Higashino M, Terao Y, Kawabata S.   Group A streptococcal cysteine protease cleaves epithelial junctions and contributes to bacterial translocation.   International conference

    11th Korea-Japan International Symposium on Microbiology 

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    Event date: 2012.9

    Language:English   Presentation type:Poster presentation  

  • 中田匡宣,住友倫子,寺尾豊,川端重忠.   A群レンサ球菌が産生するT6線毛の発現機構の解析.  

    第32回 近畿腸管微生物研究会 

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    Event date: 2012.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  • 中田匡宣,住友倫子,東野美晴,岡橋暢夫,浜田茂幸,寺尾豊,川端重忠.   Assembly mechanism of T6 pili in serotype M6 Streptococcus pyogenes.  

    第85回 日本細菌学会総会 

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    Event date: 2012.3

    Language:Japanese   Presentation type:Poster presentation  

  • Sumitomo T, Nakata M, Higashino M, Terao Y, Kawabata S.   Streptococcal pyrogenic exotoxin B contributes to cleavage of epithelial junctions.   International conference

    XVIII Lancefield International Symposium 

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    Event date: 2011.9

    Language:English   Presentation type:Poster presentation  

  • 中田匡宣,木村敬次Richard,住友倫子,寺尾豊,川端重忠.   T6線毛の形成機構とバイオフィルム形成への関与.  

    第20回 Lancefieldレンサ球菌研究会 

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    Event date: 2011.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  • Sumitomo T, Nakata M, Terao Y, Kawabata S.   Streptolysin S contributes to group A streptococcal paracellular translocation across epithelial cells.   International conference

    10th Awaji International Forum on Infection and Immunity 

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    Event date: 2010.9

    Language:English   Presentation type:Poster presentation  

  • 中田匡宣,住友倫子,磯田竜太朗,寺尾豊,川端重忠.   A群レンサ球菌が産生する線毛の細胞壁架橋機構の解析.  

    第83回 日本細菌学会総会 

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    Event date: 2010.3

    Language:Japanese   Presentation type:Poster presentation  

  • Sumitomo T, Nakata M, Terao Y, Kawabata S.   Group A Streptococci translocates across epithelial barrier via intercellular junction cleavage.   International conference

    109th General Meeting of American Society for Microbiology 

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    Event date: 2009.5

    Language:English   Presentation type:Poster presentation  

  • Isoda R, Terao Y, Nakata M, Sumitomo T, Kawabata S.   Neonatal exposure induced commensal-like immune-response against Aggregatibacter actinomycetemcomitans in mice.   International conference

    87th General Session & Exhibition of the International Association for Dental Research 

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    Event date: 2009.4

    Language:English   Presentation type:Symposium, workshop panel (public)  

  • Nakata M, Fiedler T, Koller T, Stander K, Kawabata S, Podbielski A, Kreikemeyer B.   The Nra-Ralp3 transcriptional regulatory network of Streptococcus pyogenes serotype M49: control of the novel ERES pathogenicity region.   International conference

    17th Lancefield International Symposium on Streptococci & Streptococcal Diseases 

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    Event date: 2008.6

    Language:English   Presentation type:Symposium, workshop panel (public)  

  • Nakata M, Ribardo DA, McIver KS, Podbielski A, Kreikemeyer B, Kawabata S.   Role of the Streptococcus pyogenes FCT-region components in pilus assembly and virulence.   International conference

    7th Awaji International Forum on Infection and Immunity 

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    Event date: 2007.9

    Language:English   Presentation type:Poster presentation  

  • Nakata M, Ribardo DA, McIver KS, Kawabata S, Podbielski A, Kreikemeyer B.   Role of Streptococcus pyogenes FCT-region sortase and other components in pilus assembly and virulence.   International conference

    107th General Meeting of American Society for Microbiology 

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    Event date: 2007.5

    Language:English   Presentation type:Poster presentation  

  • Nakata M, Podbielski A, Kreikemeyer B.   Analysis of a genomic island encoding important virulence factors and transcriptional regulators.   International conference

    7th ASM Conference on Streptococcal Genetics 

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    Event date: 2006.6

    Language:English   Presentation type:Poster presentation  

  • Nakagawa I, Nakata M, Sakurai A, Kawabata S, Hamada S.   Rac1-mediated invasion triggers apoptotic cell death in Streptococcus pyogenes infected epithelial cells by inducing reactive oxygen subspecies.   International conference

    105th General Meeting of American Society for Microbiology 

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    Event date: 2005.6

    Language:English   Presentation type:Poster presentation  

  • Nakata M, Kreikemeyer B, Podbielski A.   Analysis of differential recognition of surface proteins by sortase A and C2 in serotype M49 Streptococcus pyogenes.   International conference

    2nd Joint Conference of the German Society for Hygiene and Microbiology (DGHM) and the Association for General and Applied Microbiology (VAAM) 

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    Event date: 2005.2

    Language:English   Presentation type:Poster presentation  

  • Nakata M, Podbielski A, Kreikemeyer B.   MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin-mediated translocation system genes.   International conference

    2nd Joint Conference of the German Society for Hygiene and Microbiology (DGHM) and the Association for General and Applied Microbiology (VAAM) 

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    Event date: 2005.2

    Language:English   Presentation type:Symposium, workshop panel (public)  

  • Nakata M, Kreikemeyer B, Podbielski A.   The functional analysis of proteins encoded by the Group A Streptococcus pyogenes FCT region.   International conference

    Conference program for the specialized group “Microbial Pathogenicity” 

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    Event date: 2004.5

    Language:English   Presentation type:Oral presentation (general)  

  • Nakata M, Kreikemeyer B, Podbielski A.   Functional characterization of the MsmR positive regulator for fibronectin-binding by Streptococcus pyogenes.   International conference

    56th conference of the German Society for Hygiene and Microbiology (DGHM) 

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    Event date: 2004.2

    Language:English   Presentation type:Poster presentation  

  • Nakata M, Kreikemeyer B, Podbielski A.   Functional analysis of a potential polypeptide processing complex and virulence factors encoded by the Streptococcus pyogenes FCT pathogenicity region.   International conference

    56th conference of the German Society for Hygiene and Microbiology (DGHM) 

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    Event date: 2004.2

    Language:English   Presentation type:Poster presentation  

  • Nakata M, Nakagawa I, Kawabata S, Hamada S.   Overexpression of Bcl-2 can protect S. pyogenes-infected epithelial cells from apoptotic cell death.   International conference

    15th Lancefield International Symposium on Streptococci and Streptococcal Diseases 

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    Event date: 2002.10

    Language:English   Presentation type:Poster presentation  

  • Nakata M, Nakagawa I, Kawabata S, Hamada S.   Overexpression of Bcl-2 can protect Streptococcus pyogenes infected epithelial cells from apoptotic cell death.   International conference

    101st General Meeting of American Society for Microbiology 

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    Event date: 2001.5

    Language:English   Presentation type:Poster presentation  

  • Nakagawa I, Nakata M, Kawabata S, Hamada S.   Cytochrome c mediated caspase-9 activation triggers apoptosis in Streptococcus pyogenes infected epithelial cells.   International conference

    101st General Meeting of American Society for Microbiology 

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    Event date: 2001.5

    Language:English   Presentation type:Poster presentation  

  • Nakagawa I, Kimura KR, Nakata M, Kuwata H, Kawabata S, Hamada S.   A fibronectin - Fc fusion protein protects from group A streptococcal infection.   International conference

    100th General Meeting of American Society for Microbiology 

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    Event date: 2000.5

    Language:English   Presentation type:Poster presentation  

  • Nakagawa I, Kimura KR, Nakata M, Kuwata H, Kawabata S, Hamada S.   Effects of Receptor-globulins on invasive Group A Streptococcal infection.   International conference

    14th Lancefield International Symposium on Streptococci and Streptococcal Diseases 

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    Event date: 1999.10

    Language:English   Presentation type:Poster presentation  

  • Nakagawa I, Nakata M, Kawabata S, Hamada S.   Induction of apoptosis by regulated expression of the Shiga toxin B gene.   International conference

    99th General Meeting of the American Society for Microbiology 

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    Event date: 1999.5 - 1999.6

    Language:English   Presentation type:Poster presentation  

  • 窪田 星子, 中田 匡宣, 広瀬 雄二郎, 山口 雅也, 住友 倫子, 川端 重忠   血清型M49型Streptococcus pyogenesのCvfAは病原因子の発現と温度依存性の線毛産生に関与する  

    Journal of Oral Biosciences Supplement  2020.9  (一社)歯科基礎医学会

  • 李 怡萱, 中田 匡宣, 住友 倫子, 広瀬 雄二郎, 竹村 萌, 山口 雅也, 岡橋 暢夫, 川端 重忠   血清型M18型Streptococcus pyogenesのnra遺伝子に存在するナンセンス変異への点変異導入は温度依存性の線毛産生を誘導する(Restoration of intact nra transcriptional regulator into serotype M18 Streptococcus pyogenes induced thermosensitive pilus production)  

    Journal of Oral Biosciences Supplement  2019.10  (一社)歯科基礎医学会

  • 本多 真理子, 住友 倫子, Hamd Dalia, 毛利 泰士, 山口 雅也, 中田 匡宣, 川端 重忠   肺炎球菌性肺炎の発症における2コンポーネント調節系TSC08の関与(Involvement of two-component regulatory system TCS08 in pneumococcal pneumonia pathogenesis)  

    日本細菌学雑誌  2019.3  日本細菌学会

  • 竹村 萌, 山口 雅也, 広瀬 雄二郎, 住友 倫子, 中田 匡宣, 川端 重忠   肺炎球菌の菌体表層タンパク質BgaAが病態形成に果たす役割  

    日本細菌学雑誌  2020.1  日本細菌学会

  • 山口 雅也, 中田 匡宣, 住岡 龍一, 和田 聖史, 広瀬 雄二郎, 明田 幸宏, 住友 倫子, 川端 重忠   肺炎球菌のジンクメタロプロテアーゼの系統解析と髄膜炎発症に果たす役割の解明  

    日本細菌学雑誌  2017.2  日本細菌学会

  • 後藤 花奈, 山口 雅也, 広瀬 雄二郎, 住友 倫子, 中田 匡宣, 川端 重忠   肺炎球菌のコリン結合タンパク質CbpJおよびCbpLの肺炎発症における役割の解析  

    日本細菌学雑誌  2018.2  日本細菌学会

  • 山口 雅也, 広瀬 雄二郎, 後藤 花奈, 竹村 萌, 住友 倫子, 中田 匡宣, 川端 重忠   肺炎球菌のβ-ヘリックス構造タンパク質PfbAを介した貪食回避機構の解析  

    日本細菌学雑誌  2018.2  日本細菌学会

  • 竹村 萌, 山口 雅也, 後藤 花奈, 広瀬 雄二郎, 住友 倫子, 中田 匡宣, 川端 重忠   肺炎球菌のβ-ガラクトシダーゼBgaAの進化的な保存性と病態に果たす役割の解析  

    日本細菌学雑誌  2019.3  日本細菌学会

  • 広瀬 雄二郎, 山口 雅也, 後藤 花奈, 住友 倫子, 中田 匡宣, 川端 重忠   肺炎球菌のCcs4は脳血管内皮細胞への侵入に寄与する病原因子である  

    日本細菌学雑誌  2017.2  日本細菌学会

  • 高原 悠樹, 住友 倫子, 山口 雅也, 中田 匡宣, 川端 重忠   肺炎球菌が非血行性に脳へ伝播する機構の解析  

    Journal of Oral Biosciences Supplement  2020.9  (一社)歯科基礎医学会

  • 住友 倫子, 中田 匡宣, 長瀬 賢史, 高原 悠樹, 山口 雅也, 岡本 成史, 川端 重忠   病原性 インフルエンザに続発する細菌性肺炎の発症におけるGP96の機能解析  

    日本細菌学雑誌  2020.1  日本細菌学会

  • 中田 匡宣   環境に対応する微生物の生存戦略 mRNAサーモセンサーにより制御される化膿レンサ球菌の温度感受性線毛産生(Microbial strategies for survival in response to environmental factors Thermosensitive pilus production by Streptococcus pyogenes via mRNA thermosensor)  

    日本細菌学雑誌  2020.1  日本細菌学会

  • 中田 匡宣, 住友 倫子, 川端 重忠   温度感受性転写因子の翻訳効率に依存する化膿レンサ球菌の線毛発現  

    Journal of Oral Biosciences Supplement  2019.10  (一社)歯科基礎医学会

  • 山口 雅也, 後藤 花奈, 竹村 萌, 広瀬 雄二郎, 住友 倫子, 中田 匡宣, 川端 重忠   宿主と病原体が織りなす進化の謎 進化的な保存性の評価に基づく肺炎球菌の病原因子の探索  

    日本細菌学雑誌  2019.3  日本細菌学会

  • 広瀬 雄二郎, 山口 雅也, 後藤 花奈, 住友 倫子, 中田 匡宣, 川端 重忠   化膿レンサ球菌のアルギニンデイミナーゼArcAは低グルコース環境下で病原因子の発現に寄与する  

    Journal of Oral Biosciences Supplement  2018.9  (一社)歯科基礎医学会

  • 広瀬 雄二郎, 山口 雅也, 後藤 花奈, 住友 倫子, 中田 匡宣, 川端 重忠   化膿レンサ球菌のアルギニンデイミナーゼArcAは低グルコース環境下で病原因子の発現に寄与する  

    Journal of Oral Biosciences Supplement  2018.9  (一社)歯科基礎医学会

  • 本多 真理子, 住友 倫子, 山口 雅也, 中田 匡宣, 川端 重忠   化膿レンサ球菌のendopeptidase Oと補体C1qの相互作用が病原性に及ぼす影響  

    日本細菌学雑誌  2017.2  日本細菌学会

  • 中田 匡宣, 住友 倫子, 川端 重忠   化膿レンサ球菌による温度依存性の線毛産生  

    日本細菌学雑誌  2019.3  日本細菌学会

  • 中田 匡宣, 住友 倫子, 川端 重忠   化膿レンサ球菌における温度感受性の線毛発現機構  

    Journal of Oral Biosciences Supplement  2017.9  (一社)歯科基礎医学会

  • 東 孝太郎, 武部 克希, 山口 雅也, 住友 倫子, 中田 匡宣, 鈴木 守, 川端 重忠   化膿レンサ球菌におけるヒアルロン酸分解酵素の分子系統解析およびタンパク質構造解析  

    Journal of Oral Biosciences Supplement  2018.9  (一社)歯科基礎医学会

  • 広瀬 雄二郎, 山口 雅也, 秋山 徹, 竹本 訓彦, 奥野 ルミ, 山口 貴弘, 大塚 仁, 住友 倫子, 中田 匡宣, 川端 重忠   分類・疫学・感染症 Streptococcus pyogenes emm 89型の侵襲性に寄与する因子の検索  

    日本細菌学雑誌  2020.1  日本細菌学会

  • 山口 雅也, 後藤 花奈, 広瀬 雄二郎, 竹村 萌, 住友 倫子, 中田 匡宣, 川端 重忠   分子進化解析に基づく肺炎球菌のコリン結合タンパク質群の選択圧の評価  

    Journal of Oral Biosciences Supplement  2018.9  (一社)歯科基礎医学会

  • 岡橋 暢夫, 中田 匡宣, 広瀬 雄二郎, 桑田 啓貴, 川端 重忠   ミティス群レンサ球菌が産生する過酸化水素はマスト細胞の細胞死を誘導し、脱顆粒を抑制する  

    Journal of Oral Biosciences Supplement  2018.9  (一社)歯科基礎医学会

  • 花田 知己, 広瀬 雄二郎, 山口 雅也, 住友 倫子, 中田 匡宣, 川端 重忠   マウス壊死性筋膜炎モデルの感染局所におけるStreptococcus pyogenesの遺伝子発現解析  

    Journal of Oral Biosciences Supplement  2019.10  (一社)歯科基礎医学会

  • 住友 倫子, 中田 匡宣, 山口 雅也, 川端 重忠   インフルエンザ感染によるGP96シャペロンの活性化は肺炎球菌の肺胞上皮細胞への付着を亢進させる  

    Journal of Oral Biosciences Supplement  2019.10  (一社)歯科基礎医学会

  • 住友 倫子, 中田 匡宣, 山口 雅也, 川端 重忠   インフルエンザウイルス感染は化膿レンサ球菌の上皮バリア突破を亢進させる  

    日本細菌学雑誌  2017.2  日本細菌学会

  • 住友 倫子, 中田 匡宣, 山口 雅也, 川端 重忠   インフルエンザウイルス感染によるSnail1の発現誘導は化膿レンサ球菌の上皮バリア突破を亢進させる  

    Journal of Oral Biosciences Supplement  2017.9  (一社)歯科基礎医学会

  • 住友 倫子, 中田 匡宣, 長瀬 賢史, 高原 悠樹, 山口 雅也, 岡本 成史, 川端 重忠   インフルエンザに続発する細菌性肺炎の発症におけるGP96の機能解析  

    日本細菌学雑誌  2020.1  日本細菌学会

  • 李 怡萱, 中田 匡宣, 岡橋 暢夫, 山口 雅也, 住友 倫子, 川端 重忠   Streptococcus sanguinisが産生する線毛の構成因子(Component analysis of pili in Streptococcus sanguinis)  

    日本細菌学雑誌  2019.3  日本細菌学会

  • 李 怡萱, 中田 匡宣, 岡橋 暢夫, 山口 雅也, 住友 倫子, 川端 重忠   Streptococcus sanguinisが産生する細菌壁架橋型線毛の構成因子  

    Journal of Oral Biosciences Supplement  2018.9  (一社)歯科基礎医学会

  • 広瀬 雄二郎, 山口 雅也, 花田 知己, 住友 倫子, 中田 匡宣, 川端 重忠   Streptococcus pyogenesは低グルコース環境においてアルギニン代謝依存的に遺伝子発現を変動させる  

    Journal of Oral Biosciences Supplement  2019.10  (一社)歯科基礎医学会

  • 広瀬 雄二郎, 山口 雅也, 毛利 泰士, 後藤 花奈, 住友 倫子, 中田 匡宣, 川端 重忠   Streptococcus pyogenesのアルギニン代謝系が病変形成に果たす役割の解析  

    日本細菌学雑誌  2019.3  日本細菌学会

  • 広瀬 雄二郎, 山口 雅也, 毛利 泰士, 後藤 花奈, 住友 倫子, 中田 匡宣, 川端 重忠   Streptococcus pyogenesが産生するArcAは皮膚病変形成に寄与する  

    日本細菌学雑誌  2018.2  日本細菌学会

  • 山口 雅也, 広瀬 雄二郎, 竹村 萌, 大野 誠之, 住友 倫子, 中田 匡宣, 寺尾 豊, 川端 重忠   Streptococcus pneumoniaeは種特異的なタンパク質PfbAにより過剰に免疫応答を伴う宿主の死亡を抑制する  

    Journal of Oral Biosciences Supplement  2019.10  (一社)歯科基礎医学会

  • 広瀬 雄二郎, 山口 雅也, 後藤 花奈, 住友 倫子, 中田 匡宣, 川端 重忠   Streptococcus pneumoniae Ccs4は脳血管内皮細胞への付着・侵入を促進する病原因子である  

    生命科学系学会合同年次大会  2017.12  生命科学系学会合同年次大会運営事務局

  • 中田匡宣   化膿レンサ球菌におけるサーモセンサーの発見   Invited

    第3回南九州歯学会学術大会  2021 

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    Presentation type:Oral presentation (invited, special)  

  • 高原 悠樹, 住友 倫子, 河野 正充, 山口 雅也, 中田 匡宣, 保富 宗城, 川端 重忠   選抜ワークショップ3:病原性(毒素・エフェクター・生理活性物質・接着因子・定着因子) 肺炎球菌のニューモライシンによる鼻粘膜上皮バリアの傷害と脳伝播機構の解析  

    日本細菌学雑誌  2022.2  日本細菌学会

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  • 岡橋 暢夫, 沖永 敏則, 桜井 敦朗, 寺尾 豊, 中田 匡宣, 川端 重忠, 西原 達次   過酸化水素は口腔レンサ球菌の隠れた病原因子かもしれない  

    Journal of Oral Biosciences Supplement  2013.9  (一社)歯科基礎医学会

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  • 赤松 由佳子, 住友 倫子, 高原 悠樹, 山口 雅也, 中田 匡宣, 明石 満, 川端 重忠   肺炎球菌を感染させた三次元肺組織モデルにおける上皮バリアの機能障害と炎症応答の解析(Analysis of lung epithelial barrier dysfunction and inflammatory response using three-dimensional lung tissue model infected with Streptococcus pneumoniae)  

    Journal of Oral Biosciences Supplement  2022.9  (一社)歯科基礎医学会

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  • 山口 雅也, 広瀬 雄二郎, 後藤 花奈, 住友 倫子, 中田 匡宣, 川端 重忠   肺炎球菌の菌体表層タンパクPfbAは宿主の自然免疫機構からの回避に寄与する  

    Journal of Oral Biosciences Supplement  2016.9  (一社)歯科基礎医学会

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  • 高原 悠樹, 住友 倫子, 山口 雅也, 中田 匡宣, 川端 重忠, 河野 正充, 保富 宗城   肺炎球菌のニューモライシン依存的な鼻粘膜バリア傷害と脳への伝播機構の関連(Pneumolysin-dependent dysfunction of the nasal epithelial barrier is involved in pneumococcal dissemination to brain tissue)  

    Journal of Oral Biosciences Supplement  2021.10  (一社)歯科基礎医学会

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  • 毛利 泰士, 住友 倫子, 本多 真理子, 山口 雅也, 寺尾 豊, 中田 匡宣, 川端 重忠   細菌病原性の分子機序研究の最前線 Streptococcus pyogenesのシステインプロテアーゼによるデスモグレイン分解が皮膚感染症の発症に及ぼす影響  

    日本細菌学雑誌  2016.2  日本細菌学会

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  • 中田 匡宣, 住友 倫子, 浜田 茂幸, 川端 重忠   細菌の環境シグナル受容体と遺伝子調節ネットワーク Streptococcus pyogenesが産生するFCT3型線毛の発現調節機構の解析(Bacterial signal receptors and networks for gene regulation Regulation of pilus gene expression in FCT type 3 strain of Streptococcus pyogenes)  

    日本細菌学雑誌  2014.2  日本細菌学会

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  • 住友 倫子, 中田 匡宣, 寺尾 豊, 川端 重忠   細胞間隙経路を介したA群レンサ球菌の上皮細胞バリア突破機構にはストレプトリジンSが関与する(Streptolysin S contributes to group A streptococcal paracellular translocation across epithelial cells)  

    日本細胞生物学会大会講演要旨集  2010.5  (一社)日本細胞生物学会

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  • 高原 悠樹, 住友 倫子, 河野 正充, 山口 雅也, 中田 匡宣, 保富 宗城, 川端 重忠   病原因子と生態防御(感染モデル・寄生・免疫・ワクチン)/病原体と感染症 鼻咽腔に定着する肺炎球菌が非血行性に脳へ伝播する機構の解析  

    日本細菌学雑誌  2021.2  日本細菌学会

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  • 中田 匡宣, 住友 倫子, 山口 雅也, 川端 重忠   環境温度の変化に対する肺炎球菌の適応と血中における菌体生存の関連  

    Journal of Oral Biosciences Supplement  2016.9  (一社)歯科基礎医学会

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  • 中田 匡宣, 中川 一路, 川端 重忠, 浜田 茂幸   志賀毒素遺伝子を導入したマウス由来大腸菌の経口感染と宿主の応答  

    日本細菌学雑誌  1999.2  日本細菌学会

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  • 東 孝太郎, 山口 雅也, 中田 匡宣, 武部 克希, 住友 倫子, 鈴木 守, 川端 重忠   微生物の分子論(遺伝子・タンパク質・情報伝達・代謝・各種オミクス等) 結晶構造解析に基づく化膿レンサ球菌におけるヒアルロン酸分解酵素の分子機構解明  

    日本細菌学雑誌  2021.2  日本細菌学会

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  • 広瀬 雄二郎, 山口 雅也, 後藤 花奈, 住友 倫子, 中田 匡宣, 川端 重忠   形質転換誘導性タンパク質Ccs4がStreptococcus pneumoniaeの病原性に与える影響  

    Journal of Oral Biosciences Supplement  2016.9  (一社)歯科基礎医学会

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  • 山口 雅也, 広瀬 雄二郎, 住友 倫子, 中田 匡宣, 川端 重忠   常在菌と病原菌の狭間 肺炎球菌の菌体表層タンパクPfbAによる自然免疫回避機構の解析  

    日本細菌学雑誌  2016.2  日本細菌学会

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  • 東野 美晴, 住友 倫子, 中田 匡宣, 寺尾 豊, 川端 重忠   宿主細胞間接着分子の破壊に関与するA群レンサ球菌プロテアーゼの検索  

    日本細菌学雑誌  2010.2  日本細菌学会

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  • 中川 一路, 中田 匡宣, 川端 重忠, 浜田 茂幸   大腸菌志賀毒素遺伝子の細胞内導入による細胞機能の阻害メカニズムの解析  

    日本細菌学雑誌  1999.2  日本細菌学会

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  • 中田 匡宣, 住友 倫子, 山口 雅也, 川端 重忠   培養温度の変化が肺炎球菌の血中での生存に及ぼす影響  

    日本細菌学雑誌  2016.2  日本細菌学会

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  • 住友 倫子, 中田 匡宣, 山口 雅也, 川端 重忠   口腔病原体と宿主のinteraction その新たな展開 プラスミノゲンは三細胞性タイトジャンクションを介してグループA連鎖球菌の上皮転移を促進する(Interactions between oral pathogens and their hosts: new cutting edge Plasminogen promotes group A streptococcal epithelial translocation via tricellular tight junctions)  

    日本細菌学雑誌  2015.2  日本細菌学会

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  • 岡橋 暢夫, 中田 匡宣, 住友 倫子, 寺尾 豊, 川端 重忠   口腔レンサ球菌が産生する過酸化水素がマクロファージの細胞死を誘導する(Hydrogen peroxide produced by oral streptococci induces macrophage cell death)  

    日本細菌学雑誌  2014.2  日本細菌学会

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  • 岡橋 暢夫, 中田 匡宣, 桜井 敦朗, 寺尾 豊, 山口 雅也, 星野 倫範, 川端 重忠, 大嶋 隆   口腔レンサ球菌S.sanguinis線毛piliの機能  

    日本細菌学雑誌  2010.2  日本細菌学会

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  • 岡橋 暢夫, 中田 匡宣, 川端 重忠   口腔レンサ球菌2型線毛の分布とその機能  

    Journal of Oral Biosciences Supplement  2014.9  (一社)歯科基礎医学会

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  • Okahashi Nobuo, Nakata Masanobu, Terao Yutaka, Isoda Ryutaro, Sakurai Atsuo, Sumitomo Tomoko, Yamaguchi Masaya, Kimura Richard K., Oiki Eiji, Kawabata Shigetada, Ooshima Takashi   口腔のStreptococcus sanguinisの線毛は唾液アミラーゼと結合し生物膜形成を促進する(PILI OF ORAL STREPTOCOCCUS SANGUINIS BIND TO SALIVARY AMYLASE AND PROMOTE BIOFILM FORMATION)  

    日本細菌学雑誌  2011.10  日本細菌学会

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  • 東 孝太郎, 山口 雅也, 中田 匡宣, 武部 克希, 住友 倫子, 鈴木 守, 川端 重忠   化膿レンサ球菌の不活性型ヒアルロン酸分解酵素の結晶構造解析と活性型変異体の構造予測(Structural analysis of Streptococcus pyogenes hyaluronidase and in silico analysis based on structural models)  

    Journal of Oral Biosciences Supplement  2021.10  (一社)歯科基礎医学会

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  • 寺尾 豊, 川端 重忠, 中田 匡宣, 中川 一路, 浜田 茂幸   劇症型A群レンサ球菌感染症患者分離株に発現する新たなフィブロネクチン結合タンパクの解析  

    日本細菌学雑誌  2003.2  日本細菌学会

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  • 中川 一路, 黒川 顕, 中田 匡宣, 冨安 祐介, 岡橋 暢夫, 川端 重忠, 浜田 茂幸   劇症型A群レンサ球菌SSI-1株の全ゲノム解析  

    日本細菌学雑誌  2002.2  日本細菌学会

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  • 冨安 祐介, 中川 一路, 中田 匡宣, 岡橋 暢夫, 川端 重忠, 浜田 茂幸   全ゲノムPCRスキャニングによるA群S.pyogenesゲノムの比較解析  

    日本細菌学雑誌  2003.2  日本細菌学会

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  • 住友 倫子, 中田 匡宣, 毛利 泰士, 小川 真理子, 山口 雅之, 川端 重忠   インフルエンザウイルス感染に伴い上皮表層に誘導されるGP96は化膿レンサ球菌の上皮細胞への付着を亢進させる  

    Journal of Oral Biosciences Supplement  2016.9  (一社)歯科基礎医学会

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  • 中田 匡宣, 住友 倫子, 東野 美晴, 岡橋 暢夫, 浜田 茂幸, 寺尾 豊, 川端 重忠   T6線毛の組立て機構の解析(Assembly Mechanism of T6 Pili in Serotype M6 Streptococcus pyogenes)  

    日本細菌学雑誌  2012.2  日本細菌学会

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  • 住岡 龍一, 中田 匡宣, 和田 聖史, 岡橋 暢夫, 住友 倫子, 山口 雅也, 林 美加子, 川端 重忠   Stretptococcus sanguinis由来の過酸化水素は好中球にNETsを誘導する  

    日本細菌学雑誌  2016.2  日本細菌学会

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  • 岡橋 暢夫, 沖永 敏則, 桜井 敦朗, 寺尾 豊, 中田 匡宣, 川端 重忠, 西原 達次   Streptococcus sanguinisはマクロファージの泡沫化と細胞死を誘導する(Streptococcus sanguinis induces foam cell formation and cell death of macrophages)  

    日本細菌学雑誌  2013.2  日本細菌学会

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  • 中川 一路, 黒川 顕, 中田 匡宣, 川端 重忠, 浜田 茂幸   Streptococcus pyogenesゲノムのリアレンジメントによるファージ遺伝子の再構成  

    日本細菌学雑誌  2003.2  日本細菌学会

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  • 本多 真理子, 寺尾 豊, 住友 倫子, 中田 匡宣, 川端 重忠   Streptococcus pyogenesのシステインプロテアーゼSpeBによる補体免疫系回避機構  

    日本細菌学雑誌  2013.2  日本細菌学会

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  • 毛利 泰士, 住友 倫子, 中田 匡宣, 川端 重忠   Streptococcus pyogenesのC3様ADPリボシルトランスフェラーゼSpyAの機能解析  

    日本細菌学雑誌  2014.2  日本細菌学会

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  • 毛利 泰士, 住友 倫子, 山口 雅也, 中田 匡宣, 寺尾 豊, 川端 重忠   Streptococcus pyogenesに起因する皮膚感染症の発症におけるSpeBの関与  

    Journal of Oral Biosciences Supplement  2015.9  (一社)歯科基礎医学会

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  • 中田 匡宣, 中川 一路, 冨安 祐介, 川端 重忠, 浜田 茂幸   Streptococcus pyogenesにおける二成分シグナル伝達系遺伝子群の解析  

    日本細菌学雑誌  2003.2  日本細菌学会

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  • 中田 匡宣, 住友 倫子, 寺尾 豊, 浜田 茂幸, 川端 重忠   Streptococcus pyogenesが産生するFCT3型線毛の細胞壁架橋機構の解析(Cell wall anchoring mechanism of FCT region type 3 pili in Streptococcus pyogenes)  

    日本細菌学雑誌  2013.2  日本細菌学会

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  • 中田 匡宣, 住友 倫子, 浜田 茂幸, 川端 重忠   Streptococcus pyogenesが産生するFCT3型線毛の発現調節機構の解析(Regulation of pilus gene expression in FCT type 3 strain of Streptococcus pyogenes)  

    日本細菌学雑誌  2014.2  日本細菌学会

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  • 寺尾 豊, 加藤 千景, 中田 匡宣, 浜田 茂幸, 川端 重忠   Streptococcus pyogenes FbaBの細胞付着侵入および発現調節の解析  

    日本細菌学雑誌  2005.2  日本細菌学会

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  • 広瀬 雄二郎, 山口 雅也, 後藤 花奈, 住友 倫子, 中田 匡宣, 川端 重忠   Streptococcus pneumoniaeの形質転換誘導性タンパクCcs4は病原因子として働く  

    日本細菌学雑誌  2016.2  日本細菌学会

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  • 寺尾 豊, 山口 雅也, 中田 匡宣, 浜田 茂幸, 川端 重忠   Streptococcus pneumoniaeに対するキメラ免疫グロブリン製剤の構築  

    Journal of Oral Biosciences  2007.8  (一社)歯科基礎医学会

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  • 中田 匡宣, 住友 倫子, 寺尾 豊, 川端 重忠   M6型A群レンサ球菌が産生するFCT1型線毛遺伝子の転写調節  

    日本細菌学雑誌  2015.2  日本細菌学会

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  • 山口 雅也, 中田 匡宣, 住友 倫子, 川端 重忠   M4型Streptococcus pyogenesのヒアルロン酸分解酵素が宿主細胞内生存に果たす役割  

    日本細菌学雑誌  2015.2  日本細菌学会

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  • 冨安 祐介, 中川 一路, 中田 匡宣, 川端 重忠, 浜田 茂幸   EGFP高発現A群レンサ球菌を用いた宿主細胞への付着・侵入能の解析  

    日本細菌学雑誌  2001.2  日本細菌学会

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  • Ara Takahide, Ota Shuichi, Shima Kanako, Yasumoto Atsushi, Minauchi Koichiro, Obara Masato, Nakata Masanobu, Imai Kiyotoshi, Hirano Teiichi, Ogasawara Masahiro, Kiyama Yoshio, Kobayashi Naoki, Imamura Masahiro   Cefepimeに治療不応性の発熱性好中球減少症患者に対するABK投与とVCM投与とを比較する前向き無作為化研究(Prospective randomized study of ABK vs VCM for febrile neutropenic patients in refractory to CFPM)  

    臨床血液  2013.9  (一社)日本血液学会-東京事務局

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  • 作田 哲也, 大貝 悠一, 中田 匡宣   Candida albicansの増殖とバイオフィルム形成に対するフロリジンの影響  

    日本細菌学雑誌  2021.2  日本細菌学会

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  • 小川 真理子, 住友 倫子, 毛利 泰士, 山口 雅也, 中田 匡宣, 川端 重忠   C1qとの相互作用を介する化膿レンサ球菌の補体免疫回避機構  

    Journal of Oral Biosciences Supplement  2016.9  (一社)歯科基礎医学会

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  • 住友 倫子, 中田 匡宣, 山口 雅也, 川端 重忠   Bacteria meet Viral Infection インフルエンザウイルス感染に伴うGp96の局在と化膿レンサ球菌感染症の関連性  

    日本細菌学雑誌  2016.2  日本細菌学会

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  • 住友 倫子, 東野 美晴, 中田 匡宣, 川端 重忠   A群連鎖球菌は三細胞間タイトジャンクションを介して上皮のバリアを越えて移動する(Group A Streptococcus translocates across epithelial barrier via tricellular tight junctions)  

    日本細菌学雑誌  2014.2  日本細菌学会

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  • 中田 匡宣, 住友 倫子, 寺尾 豊, 川端 重忠   A群レンサ球菌線毛の温度感受性発現機構の解析  

    日本細菌学雑誌  2009.2  日本細菌学会

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  • 中田 匡宣, 住友 倫子, 寺尾 豊, 川端 重忠   A群レンサ球菌線毛の機能解析  

    日本細菌学雑誌  2008.2  日本細菌学会

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  • 中田 匡宣, 中川 一路, 川端 重忠, 浜田 茂幸   A群レンサ球菌感染による上皮細胞のアポトーシスとその制御機構  

    日本細菌学雑誌  2001.2  日本細菌学会

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  • 住友 倫子, 中田 匡宣, 寺尾 豊, 川端 重忠   A群レンサ球菌は宿主カルパインの活性化を介して上皮バリアを突破する  

    Journal of Oral Biosciences Supplement  2013.9  (一社)歯科基礎医学会

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  • 住友 倫子, 中田 匡宣, 寺尾 豊, 川端 重忠   A群レンサ球菌の分泌型システインプロテアーゼであるSpeBは上皮細胞間接着分子を分解する  

    Journal of Oral Biosciences  2011.9  (一社)歯科基礎医学会

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  • 中川 一路, 中田 匡宣, 川端 重忠, 浜田 茂幸   A群レンサ球菌の侵入によるヒト上皮細胞における遺伝子発現の解析  

    日本細菌学雑誌  2000.4  日本細菌学会

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  • 住友 倫子, 中田 匡宣, 東野 美晴, 寺尾 豊, 川端 重忠   A群レンサ球菌の上皮バリア突破機構に関与する宿主プロテアーゼの解析  

    日本細菌学雑誌  2010.2  日本細菌学会

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  • 住友 倫子, 中田 匡宣, 寺尾 豊, 川端 重忠   A群レンサ球菌の上皮バリア突破機構に関する解析  

    日本細菌学雑誌  2009.2  日本細菌学会

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  • 中田 匡宣, 中川 一路, 川端 重忠, 浜田 茂幸   A群レンサ球菌のヒト上皮細胞への侵入によるアポトーシス誘導機構の解析  

    日本細菌学雑誌  2000.4  日本細菌学会

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  • 住友 倫子, 東野 美晴, 小南 明里, 中田 匡宣, 寺尾 豊, 川端 重忠   A群レンサ球菌のシステインプロテアーゼSpeBおよびSib35による上皮細胞間接着分子の分解(Group A streptococcal cysteine proteases, SpeB and Sib35, cleave epithelial junctions)  

    日本細菌学雑誌  2013.2  日本細菌学会

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  • 本多 真理子, 住友 倫子, 毛利 泰士, 山口 雅也, 中田 匡宣, 川端 重忠   A群レンサ球菌のendopeptidase Oによる補体C1qを介した補体免疫回避機構  

    日本細菌学雑誌  2016.2  日本細菌学会

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  • 中川 一路, 中田 匡宣, 冨安 祐介, 川端 重忠, 浜田 茂幸   A群レンサ球菌による上皮細胞死誘導機構の解析  

    日本細菌学雑誌  2002.2  日本細菌学会

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  • 中田 匡宣, 寺尾 豊, 川端 重忠   A群レンサ球菌が産生する線毛の機能解析  

    Journal of Oral Biosciences  2008.9  (一社)歯科基礎医学会

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  • 高原 悠樹, 住友 倫子, 河野 正充, 赤松 由佳子, 山口 雅也, 中田 匡宣, 保富 宗城, 川端 重忠.   肺炎球菌のニューモライシン依存的な鼻粘膜上皮バリア傷害と脳伝播機構の解析.  

    第52回 レンサ球菌研究会  2022.7 

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    Venue:仙台市  

  • 大貝 悠一, 松本 愛理, 中田 匡宣   F.nucleatum表層タンパクFap2及びCmpAはA.actinomycetemcomitansとの共培養バイオフィルム形成を促進する(Fap2 and CmpA enhance coculture biofilm formation between F.nucleatum and A.actinomycetemcomitans)  

    日本細菌学雑誌  2026.3  日本細菌学会

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  • 武部 克希, 宮川 柊兵, 小林 弘子, 中田 匡宣   見えた!細菌の生命現象-細菌学研究を進展させるマクロからミクロの構造にまつわる技術 X線構造解析を基軸とした微生物タンパク質の構造及び機能解析  

    日本細菌学雑誌  2026.3  日本細菌学会

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  • 住岡 龍一, 中田 匡宣, 森田 知里, 野杁 由一郎, 川端 重忠, 林 美加子   口腔常在レンサ球菌が産生する細胞外ヌクレアーゼの機能解析  

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集  2013.5  (NPO)日本歯科保存学会

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  • 岡橋 暢夫, 中田 匡宣, 住友 倫子, 桜井 敦朗, 桑田 啓貴, 川端 重忠   口腔レンサ球菌が産生する過酸化水素は上皮細胞に対する細胞傷害性を有する  

    Journal of Oral Biosciences Supplement  2015.9  (一社)歯科基礎医学会

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  • 山口 雅也, 東 孝太郎, 武部 克希, 中田 匡宣, 住友 倫子, 川端 重忠   化膿連鎖球菌の不活性ヒアルロニダーゼの構造解析(Structural analysis of inactive hyaluronidase of Streptococcus pyogenes)  

    日本細菌学雑誌  2024.7  日本細菌学会

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  • 東 孝太郎, 山口 雅也, 武部 克希, 中田 匡宣, 住友 倫子, 川端 重忠, 鈴木 守   化膿レンサ球菌のヒアルロン酸分解酵素HylAに関する構造生物学を中心とした機能解析  

    Journal of Oral Biosciences Supplement  2024.11  (一社)歯科基礎医学会

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  • 中田 匡宣, 窪田 星子, 広瀬 雄二郎, 山口 雅也, 住友 倫子, 川端 重忠   化膿レンサ球菌のRNase Yによる線毛産生量の調節  

    Journal of Oral Biosciences Supplement  2023.9  (一社)歯科基礎医学会

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  • 右田 裕乃, 松本 愛理, 大貝 悠一, 中田 匡宣   化膿レンサ球菌における温度感受性ScpA産生機構の解析  

    Journal of Oral Biosciences Supplement  2025.9  (一社)歯科基礎医学会

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  • 赤松 由佳子, 住友 倫子, 高原 悠樹, 広瀬 雄二郎, 山口 雅也, 中田 匡宣, 秋山 茂久, 明石 満, 川端 重忠   三次元肺組織モデルを用いた肺炎球菌感染が引き起こす上皮バリア傷害の解析  

    Journal of Oral Biosciences Supplement  2025.9  (一社)歯科基礎医学会

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  • 松本 愛理, 大貝 悠一, 住友 倫子, 中田 匡宣, 田端 厚之   ミティス群レンサ球菌が産生する細胞外小胞の作用特性の解明  

    Journal of Oral Biosciences Supplement  2023.9  (一社)歯科基礎医学会

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  • 松本 愛理, 大貝 悠一, 住友 倫子, 田端 厚之, 中田 匡宣   ストレプトコッカス・ミティスの膜小胞の生成と機能的特性(Production and functional characteristics of membrane vesicles in Streptococcus mitis)  

    日本細菌学雑誌  2025.4  日本細菌学会

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  • 三浦 滉毅, 中田 匡宣, 西谷 佳浩   キトサン含有新規抗菌歯科材料の開発に向けた,口腔内微生物に対するキトサンの抗菌活性と有用性の探索  

    日本歯科医学会誌  2024.3  日本歯科医学会

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  • 住岡 龍一, 森田 知里, 中田 匡宣, 岡橋 暢夫, 住友 倫子, 川端 重忠   Streptococcus sanguinisの菌体表層ヌクレアーゼは自然免疫からの回避に寄与する  

    Journal of Oral Biosciences Supplement  2013.9  (一社)歯科基礎医学会

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  • 森田 知里, 住岡 龍一, 中田 匡宣, 和田 聖史, 岡橋 暢夫, 住友 倫子, 山口 雅也, 浜田 茂幸, 山城 隆, 川端 重忠   Streptococcus sanguinisの細胞壁架橋型ヌクレアーゼの酵素活性  

    Journal of Oral Biosciences Supplement  2014.9  (一社)歯科基礎医学会

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  • 森田 知里, 住岡 龍一, 中田 匡宣, 岡橋 暢夫, 本多 真理子, 住友 倫子, 川端 重忠   Streptococcus sanguinisの細胞壁架橋型ヌクレアーゼの機能解析  

    日本細菌学雑誌  2013.2  日本細菌学会

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  • 住岡 龍一, 中田 匡宣, 野杁 由一郎, 川端 重忠, 林 美加子   Streptococcus sanguinisが産生する過酸化水素は好中球の細胞死を誘導する  

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集  2014.10  (NPO)日本歯科保存学会

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  • 住岡 龍一, 中田 匡宣, 森田 知里, 和田 聖史, 岡橋 暢夫, 住友 倫子, 山口 雅也, 林 美加子, 川端 重忠   Streptococcus sanguinisが産生する過酸化水素はNETs形成を誘導する  

    Journal of Oral Biosciences Supplement  2014.9  (一社)歯科基礎医学会

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  • 武部 克希, 鈴木 守, 東 孝太郎, 山口 雅也, 住友 倫子, 川端 重忠, 中田 匡宣   Streptococcus sanguinisが産生する線毛タンパク質のX線結晶構造解析  

    Journal of Oral Biosciences Supplement  2023.9  (一社)歯科基礎医学会

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  • 森田 知里, 住岡 龍一, 中田 匡宣, 住友 倫子, 岡橋 暢夫, 浜田 茂幸, 川端 重忠   Streptococcus sanguinisが産生する細胞壁架橋型ヌクレアーゼによる免疫回避機構(Wall-anchored nuclease of Streptococcus sanguinis contributes to evasion of innate immunity)  

    日本細菌学雑誌  2014.2  日本細菌学会

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  • 岡橋 暢夫, 中田 匡宣, 桑田 啓貴, 川端 重忠   Streptococcus oralis由来の過酸化水素はマクロファージのリソソームを傷害する  

    Journal of Oral Biosciences Supplement  2016.9  (一社)歯科基礎医学会

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  • 松本 愛理, 大貝 悠一, 住友 倫子, 田端 厚之, 中田 匡宣   Streptococcus mitisが産生するメンブランベシクルの作用特性  

    Journal of Oral Biosciences Supplement  2024.11  (一社)歯科基礎医学会

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  • 山口 雅也, 中田 匡宣, 広瀬 雄二郎, 後藤 花奈, 住友 倫子, 川端 重忠   Streptococcus agalactiaeのシアル酸分解酵素に着目した分子進化解析  

    Journal of Oral Biosciences Supplement  2015.9  (一社)歯科基礎医学会

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  • 山口 雅也, 中田 匡宣, 広瀬 雄二郎, 後藤 花奈, 住友 倫子, 川端 重忠   Streptococcus agalactiaeのシアル酸分解酵素に着目した分子進化解析  

    Journal of Oral Biosciences Supplement  2015.9  (一社)歯科基礎医学会

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  • 田中 友三佳, 大貝 悠一, 中田 匡宣, 野口 和行   Fusobacterium nucleatumとAggregatibacter actinomycetemcomitansの共凝集メカニズムの解析  

    日本歯周病学会会誌  2024.10  (NPO)日本歯周病学会

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  • 田中 友三佳, 大貝 悠一, 松本 愛理, 中田 匡宣   Fusobacterium nucleatumがFap2を介してAggregatibacter actinomycetemcomitansと共凝集する機構の解析  

    Journal of Oral Biosciences Supplement  2023.9  (一社)歯科基礎医学会

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  • 山口 雅也, 中田 匡宣, 住友 倫子, 川端 重忠   A群レンサ球菌のヒアルロン酸分解酵素が病原性に果たす役割  

    Journal of Oral Biosciences Supplement  2014.9  (一社)歯科基礎医学会

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  • 山口 雅也, 中田 匡宣, 住友 倫子, 川端 重忠   A群レンサ球菌のヒアルロン酸分解酵素が病原性に果たす役割  

    Journal of Oral Biosciences Supplement  2014.9  (一社)歯科基礎医学会

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  • 中田 匡宣, 寺尾 豊, 川端 重忠   A群レンサ球菌が産生する線毛の発現機構の解析  

    Journal of Oral Biosciences  2009.8  (一社)歯科基礎医学会

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  • 中田 匡宣, 川端 重忠   A群レンサ球菌Pilus発現機構の解析  

    日本細菌学雑誌  2007.2  日本細菌学会

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  • 大貝 悠一, 藤田 愛弓, 中田 匡宣, 小松澤 均   Aggregatibacter actinomycetemcomitansは血清培養時に共凝集性を促進する  

    日本細菌学雑誌  2021.2  日本細菌学会

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  • 大貝 悠一, 松本 愛理, 中田 匡宣   A.actinomycetemcomitansのバイオフィルム形成はHfqによって制御される遺伝子発現と関連している(Biofilm formation of A. acitnomycetemcomitans associates with genes expression regulated by Hfq)  

    日本細菌学雑誌  2024.6  日本細菌学会

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Awards

  • 大阪大学総長奨励賞 2015

    2015.7   大阪大学  

    中田 匡宣

Research Projects

  • BacPROTACsを活用した歯周病原性バイオフィルム制御技術の創生

    Grant number:24K22190  2024.6 - 2027.3

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    住友 倫子, 中田 匡宣

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    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

  • 歯周病原因細菌の口腔から全身への定着に関与する因子の研究

    Grant number:23K09141  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    大貝 悠一, 中田 匡宣, 松本 愛理

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

  • 経口糖尿病治療薬であるSGLT-2阻害薬がカンジダ・アルビカンスに及ぼす影響

    Grant number:23K09462  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    作田 哲也, 中田 匡宣, 藤島 慶

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    ■研究の背景と目的:糖尿病の新しい治療薬であるSGLT-2阻害薬(ナトリウム-グルコース共輸送体阻害薬)には腎臓や心臓の機能を保護する効果が知られていますが、現在のところ口内炎や口腔内の感染に対してどのような働きがあるかについては十分にはわかっていません。本研究では、実験的に糖尿病を引き起こすことのできるラットを用いた実験と培養細胞を用いた実験によって、口腔内に感染症を引き起こす真菌(カビの一種)に対するSGLT-2阻害薬の影響を調べ、SGLT-2阻害薬が<口腔内の健康状態を保つ>ことに役に立つのかどうかについて明らかにしていきます。
    ■研究方法:同じ舌より採取された真菌であるカンジダ・アルビカンスとカンジダ・グラブラータを供試し共培養下でのバイオフィルム形成を調べました。カンジダ・アルビカンスとカンジダ・グラブラータはどちらも「入れ歯」を原因とする口内炎を引き起こすだけでなく血液を介して全身に達すると重篤なカンジダ血症の原因となります。真菌がバイオフィルムを形成すると①真菌に作用する薬剤の効きが悪くなる②バイオフィルム自体が感染源となって全身に広がる③バイオフィルム自体を除去することが困難等の理由で感染症が重くなる場合があります。
    ■結果:1)カンジダ・グラブラータと比較するとカンジダ・アルビカンスのバイオフィルム形成量は多くなりました。2)カンジダ・アルビカンスのバイオフィルム形成量はカンジダ・グラブラータが共存すると増強されました。

  • 口腔内の病原性共生細菌に対する一本鎖可変断片の創生と応用

    Grant number:22K19633  2022.6 - 2025.3

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    中田 匡宣, 大貝 悠一, 松本 愛理

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    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

  • RNAサーモセンサーとタンパク質重合体を介するレンサ球菌感染機構の探索

    Grant number:23K24521  2022.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    中田 匡宣, 松本 愛理, 大貝 悠一

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    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

    グラム陽性病原細菌が産生する線毛は,複数のサブユニットがイソペプチド結合で連結するタンパク質重合体であり,宿主への付着因子として機能する.口腔細菌であるStreptococcus sanguinis は感染性心内膜炎の起因菌となる病原性共生細菌の一種である.一方,化膿レンサ球菌は主に上気道と皮膚に化膿性炎症を惹起する.本研究では,S. sanguinisと化膿レンサ球菌が産生する線毛の組み立て機構と機能の解明を目的とした.S. sanguinis の線毛については,線毛先端に位置するサブユニットの連結機構について明らかにし,構造解析を行った.また,親和性を有する細胞外マトリックスタンパク質の検索を行った.化膿レンサ球菌の線毛については,血清型M3/T3株の線毛基部サブユニットについて,X 線結晶構造解析を行い,構造を決定した.免疫グロブリン様ドメインとプロリンに富むテール領域から構成され,分子内の広範囲に渡る疎水性相互作用によって構造が安定化されることを明らかにした.また,既報の構造との比較により,オメガループ構造とテール領域の方向性に主な違いが認められた.オメガループ内に存在し,他の線毛サブユニットとのイソペプチド結合を担うリジン残基は両構造で同位置にある一方で,オメガループ内の水素結合ネットワークに違いが認められたことから,リジン残基の位置変化を伴わない水素結合ネットワークの変化が他の線毛サブユニットへの連結を促進すると考えられた.また,テール領域の方向性の違いは,テール領域基部に位置するアミノ酸一残基の違いに起因する可能性が示唆された.さらに,線毛基部サブユニットと他の線毛サブユニットの連結には推定シャペロンが必要であることを明らかにした.

  • RNAサーモセンサーとタンパク質重合体を介するレンサ球菌感染機構の探索

    Grant number:22H03263  2022.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    中田 匡宣, 大貝 悠一, 松本 愛理

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    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

  • プロバイオティクスが覚醒時ブラキシズムと顎関節症に及ぼす影響の解明

    Grant number:22K10252  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    大迫 佑季, 福嶋 美佳, 渡邉 温子, 宮脇 正一, 前田 綾, 大賀 泰彦, 井戸 章雄, 上村 修司, 中田 匡宣

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    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

  • 一細胞解析による肺炎球菌感染時の宿主転写応答の解明

    Grant number:20K21675  2020.7 - 2023.3

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    川端 重忠, 山口 雅也, 住友 倫子, 中田 匡宣

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    Grant amount:\6370000 ( Direct Cost: \4900000 、 Indirect Cost:\1470000 )

    口腔レンサ球菌の一種である肺炎球菌は、肺炎の主たる起因菌である。肺炎球菌性肺炎では、宿主の過剰な炎症応答が組織を破壊し、菌が深部へ伝播すると考えられている。一方で、感染によりどのような細胞集団が遊走されるか、また細胞集団が感染にそれぞれどのように応答しているのか、詳細な情報は今まで明らかとなっていない。本研究は、感染によって引き起こされる宿主のRNA転写およびゲノムワイドのオープンクロマチン領域の変化を細胞集団ごとに解析することで、これまでにない精度での宿主応答の解明手段の確立を試みるものである。
    今年度においては、マウス肺炎モデルから得た肺胞洗浄液について、細胞デブリを密度勾配遠心により除き、死細胞を磁気標識してマグネットを用いて除去することを試みた。しかし、シングルセル解析を実施するのに十分な数と品質の細胞を確保することができなかった。肺胞洗浄液ではなく、肺全体を懸濁することも視野に入れ、引き続き細胞の回収方法を検討する。さらに、感染時には血液から感染局所に炎症細胞が遊走すると考えられることから、必要に応じて血液を検体としてシングルセル解析を試みる。
    また、半数致死量以下の菌数を感染し、感染後の肺組織について炎症応答を解析したところ、炎症性サイトカイン量は感染前と比較して有意な増加が認められないことが示された。一方で、肺組織中の好中球エラスターゼ発現細胞の割合は増加した。このことから、肺炎球菌は宿主の免疫細胞を介さずに直接的に好中球を活性化する可能性が示された。

  • 歯周病原因菌の病原性因子及び挿入配列を制御するsmall RNAの解析

    Grant number:20K09922  2020.4 - 2023.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    大貝 悠一, 中田 匡宣, 小松澤 均

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    Aggregatibacter actinomycetemcomitansのsmall RNA発現性の解析を目的とし、2成分制御系の欠損株作製を行った。2成分制御系因子は細菌特有の遺伝子発現制御系であり、菌体表層のセンサータンパクにより外環境の変化を感知し、細胞質内のレギュレータータンパクをリン酸化し、様々な遺伝子の発現制御を行う。他細菌において、2成分制御系がsmall RNAの発現制御を行う例も知られていることから、本菌においても検討を行う。これまでにAggregatibacter actinomycetemcomitans ATCC29523, NUM4039株などにおいて見られる2成分制御系の欠損株を各3株作製している。今後、それらの欠損株において発現変動を示すsmall RNAを個別に解析する。
    Fusobacteirum nucleatumは歯周病原因菌の一つである。本菌は他細菌と結合する(共凝集)ことにより、口腔内のプラーク成熟に重要な役割を持つと考えられている。当研究では本菌にも着目し、small RNAを介した遺伝子発現制御に関わるHfqタンパクやその他2成分制御系などのレギュレーターの遺伝子欠損株の作製を検討している。本菌における遺伝子欠損はATCC 23726株において報告がある。これまでにクロラムフェニコール耐性遺伝子を挿入させる手法により、他細菌との共凝集に関与する表層タンパクの欠損株作製に成功している。今後、本菌におけるsmall RNAの新規同定と併せ、small RNAやsmall RNAの制御因子の欠損株作製を行う。

  • Investigation of novel infection control strategy based on bacterial evolutional information

    Grant number:19K22710  2019.6 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    Yamaguchi Masaya

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    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

    In this study, we attempted to establish novel strategy for identification of drug targets based on bacterial evolutionary analysis.
    Our evolutionary analysis showed that among the examined pneumococcal genes, nanA and bgaA had high proportions of codon that were under significant negative selection. In addition, our in vitro and in vivo analyses indicated that BgaA works as a virulence factor via inducing vascular injury and blood coagulation.
    Concerning Streptococcus pyogenes, our genome-wide association study using 351 genomes of S. pyogenes detected several genes and single nucleotide polymorphisms involved in the invasiveness.

  • Molecular mechanisms underlying streptococcal infections for development of preventive and therapeutic measures

    Grant number:19H03825  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Kawabata Shigetada

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    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

    Streptococcus pyogenes and Streptococcus pneumoniae are major human-specific bacterial pathogens that causes a wide array of manifestations ranging from mild localized infections to life-threatening invasive infections. These streptococcal species were also identified as the predominant pathogens that cause bacterial pneumonia following influenza. To clarify the mechanism responsible for viral infection-induced enhancement of bacterial adherence to host cells, we identified both host and bacterial factors involved in that process. We then utilized an in vivo model to investigate whether the identified host and bacterial factors involved in the pathogenesis of coinfection are useful targets for development of therapeutic strategies.

  • 細菌における新規翻訳制御機構の探索

    2019 - 2020

    日本学術振興会  挑戦的研究(萌芽) 

    中田 匡宣

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    Authorship:Principal investigator  Grant type:Competitive

  • Exploration of a novel dissemination route for development of therapeutic strategies against bacterial meningitis

    Grant number:18K19643  2018.6 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    Kawabata Shigetada

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    Grant amount:\6240000 ( Direct Cost: \4800000 、 Indirect Cost:\1440000 )

    Bacterial meningitis is considered to be caused by bacteremia, and then leads to blood-brain barrier disruption and dissemination of bacteria into the central nervous system. To investigate the mechanism by which Streptococcus pneumoniae, a colonizer of the nasopharynx, spreads to brain tissue, we utilized strain EF3030, clinically isolated from otitis media, for construction of a murine infection model. While neither bacteremia nor pneumonia was observed in this model, pneumococci were isolated from the frontal olfactory bulb, caudal cerebrum, and cerebellum. Notably, deletion of the ply gene encoding pneumolysin markedly compromised the ability of the organisms to disseminate into brain tissue. Taken together, our findings indicate that pneumolysin allows S. pneumoniae to disseminate from the nasopharynx into brain tissue in a non-hematogenous manner via the olfactory nerve pathway.

  • Infection by oral mitis group streptococci induces impairment of mast cell function and allergic response

    Grant number:17K11958  2017.4 - 2021.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Okahashi Nobuo

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    Mast cells play central roles in allergic reaction. In this study, we found that H2O2 produced by mitis group streptococci such as Streptococcus oralis reduced degranulation of mast cells stimulated with IgE-antigen complex. The reduction of the degranulation was related to the H2O2-induced cell death. Lysosomal dysfunction by H2O2 seemed to contribute to the unique cell death. Using mouse model of pollen allergy, we found that streptococcus-derived H2O2 reduced the sneezing of the sensitized mice challenged with cedar pollen. These results suggest that H2O2 produced by the oral mitis group streptococci is able to disrupt the host allergic reaction.
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  • Streptococcal translocation across epithelial barrier via tricellular junction

    Grant number:17K11610  2017.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Sumitomo Tomoko

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    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    Streptococcus pyogenes is responsible for a wide variety of cutaneous infections ranging from superficial impetigo to fulminant invasive necrotizing fasciitis. Dysfunction of desmosomes is associated with the pathogenesis of cutaneous diseases. We identified streptococcal pyrogenic exotoxin B (SpeB) as a proteolytic factor that cleaves the extracellular domains of desmoglein 1 and 3. In an epicutaneous infection model, lesional skin infected with an speB deletion mutant were significantly smaller as compared to those caused by the wild-type strain. Our findings provide evidence that SpeB-mediated degradation of desmosomes has a pathogenic role in development of S. pyogenes cutaneous infection. Furthermore, we found that that interaction of HtpA with LSR, a major component of tricellular junctions, is crucial for bacterial localization. Our data suggest that S. pyogenes exploits host LSR for acceleration of bacterial invasion into deeper tissues via tricellular junctions.

  • レンサ球菌のニッチ拡大に伴う宿主-菌体相互作用の解析

    2017 - 2019

    日本学術振興会  基盤研究(B) 

    中田 匡宣

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    Authorship:Principal investigator  Grant type:Competitive

  • 菌体表層に存在する線維状タンパク質重合体の会合と抗原性がもたらす病原性の探索

    2017 - 2018

    日本学術振興会 

    中田 匡宣

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    Authorship:Principal investigator  Grant type:Competitive

  • Molecular epidemiological analysis of Streptococcus pneumoniae in Southeast Asian countries

    Grant number:16H05847  2016.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Kawabata Shigetada

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    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

    Pneumococcal infection is a major cause of death, especially in children and older people. Streptococcus pneumoniae shows high competence and imports genes encoding drug resistance and virulence factors. In this study, we attempt to correct clinical strains in Thailand and Myanmar, and analyze those molecular epidemiological information. In Thailand, we collected 440 strains of oral streptococcal bacteria isolated from healthy people. In Myanmar, we collected 300 specimens from acute respiratory infection patients. We performed several biochemistry tests and selected 60 pneumococcal candidates. Next generation sequencing analysis showed that the distribution of serotypes, sequence types, antimicrobial resistance genes and virulence factors. The information would contribute to the prevention and treatment of pneumococcal disease and in Japan.

  • Role of streptococcal arginie deiminase in the evasion of host immunity

    Grant number:16K15787  2016.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    Yamaguchi Masaya

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    Grant amount:\3510000 ( Direct Cost: \2700000 、 Indirect Cost:\810000 )

    Members of the genus Streptococcus are major constituents of human skin and the mucosal microbiome, of which some, such as Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae, are extracellular pathogens that occasionally cause life-threatening infectious diseases. In this study, we focused on the role of streptococcal arginie deiminase in the evasion of host immunity. In pilot study, S. pyogenes produced higher amount of ammonium ion as compared to S. pneumoniae and S. agalactiae. Next, we performed mouse infection assay using S. pyogenes wild-type and arginine deiminase knock out strains. The infection assay indicated that S. pyogenes-arginine deiminase pathway contributes to the pathogenesis in the skin infection.

  • レンサ球菌が産生する線毛の付着機能と発現機構の解析

    2016 - 2019

    日本学術振興会  国際共同研究加速基金(国際共同研究強化) 

    中田 匡宣

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    Authorship:Principal investigator  Grant type:Competitive

  • Exploration of streptococcal factors related with onset of bacteremia and systemic dissemination

    Grant number:15H05012  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KAWABATA SHIGETADA

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    Grant amount:\17030000 ( Direct Cost: \13100000 、 Indirect Cost:\3930000 )

    During the onset of invasive streptococcal diseases, bacteria systemically disseminate via the bloodstream. The exact mechanism by which pathogenic streptococci evade host immunity and disseminate to the bloodstream remains elusive. In this study, we revealed factors of pathogenic streptococci, including Streptococcus pneumoniae, Streptococcus pyogenes, and oral streptococci, involved in tissue invasion, immune evasion, and bacterial survival in the blood stream.

  • Analysis of streptococcal translocation across epithelial barrier via paracellular route

    Grant number:26462780  2014.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Sumitomo Tomoko

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    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    Streptococcus pyogenes is a human-specific pathogen responsible for local suppurative and life-threatening invasive systemic diseases. In the present study, a serotype M28 strain was found predominantly localized in tricellular tight junctions (tTJs) of epithelial cells cultured in the presence of plasminogen (PLG). Several lines of evidence indicated that interaction of PLG with tricellulin, a major component of tTJs, is crucial for bacterial localization. Additionally, we demonstrated that PLG functions as a molecular bridge between tricellulin and streptococcal surface enolase (SEN). The wild type strain efficiently translocated across the epithelial monolayer, accompanied by cleavage of transmembrane junctional proteins. In contrast, amino acid substitutions in the PLG-binding motif of SEN markedly compromised those activities. Our findings provide insight into the mechanism by which S. pyogenes exploits host PLG for acceleration of bacterial invasion into deeper tissues via tTJs.

  • Pathogenicity of hydrogen peroxide produced by oral streptococci

    Grant number:26463112  2014.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Okahashi Nobuo, KUWATA Hirotaka

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    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    Members of the oral mitis group streptococci are dominant colonizers of dental plaque, and causative agents of infective endocarditis.
    In the present study, we found that these streptococci produce hydrogen peroxide (H2O2), which is cytotoxic to human macrophages and neutrophils. The cytotoxic effect seemed to be independent of inflammatory responses, because H2O2 was not a potent stimulator of inflammatory cytokines such as TNF-a in macrophages. Our study reveals that streptococcal H2O2 plays as a cytotoxin, and is implicated in the evasion of these streptococci from host defense system by inducing cell death of innate immune cells.

  • Analysis of ornithine rhamnolipid-like pigment from oral bacteria

    Grant number:26670800  2014.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    Kawabata Shigetada, NAKATA Masanobu, SUMITOMO Tomoko, YAMAGUCHI Masaya

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    Grant amount:\3640000 ( Direct Cost: \2800000 、 Indirect Cost:\840000 )

    Pigments are produced from numerous bacterial species. Although several pigments possess hemolytic and cytotoxic properties, their roles in virulence of bacterial pathogens is not fully appreciated. In this study, we found that GNAT (GCN5-related N-acetyltransferase) is related to ornithine rhamnolipid-like pigment synthesis of Propionibacterium acnes. Moreover, we demonstrated that the pigmentation is responsible for their hemolytic activity. P. acnes is known to be associated with sarcoidosis. Our results suggest that targeting of P. acnes pigment could serve as a novel strategy to treatment for sarcoidosis.

  • Exploration of bacterial factors that inactivate complement regulatory factors and induce invasive infectious diseases

    Grant number:24390410  2012.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KAWABATA Shigetada, TERAO Yutaka, SUMITOMO Tomoko, NAKATA Masanobu

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    Grant amount:\17940000 ( Direct Cost: \13800000 、 Indirect Cost:\4140000 )

    Evasion of the human immune system is a hallmark of pathogenic streptococci that cause invasive infections, and leads to exacerbation of pathological condition during the course of infection. In this study, we revealed that a group A streptococcal protease, SpeB, cleaves C1 esterase inhibitor, and the cleavage is attributable to bacterial survival and aberration of complement system. Moreover, we demonstrate a mechanism by which streptococcus species frequently isolated from subacute bacterial endocarditis evades neutrophil killing.

  • Role of cyclodextrin in oral bacteria-associated systemic illness

    Grant number:24659812  2012.4 - 2014.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    KAWABATA SHIGETADA, TERAO Yutaka, NAKATA Masanobu, SUMITOMO Tomoko

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    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

    Alpha-glucans such as starch and glycogen are abundant in the human oral cavity. Degradation of alpha-glucans by alpha-glucanotransferase (CGTase) enzymes leads to the clodextrins (CDs) production. CDs induce a cholesterol-depleted membrane and a destabilization of the barrier function of tight junctions in host cells. We demonstrated that Porphyromonas gingivalis, a periodontal pathogen, utilizes alpha-glucans to produce CDs. Our data suggest that P. gingivalis-produced CDs contribute to the pathogenesis of oral bacteria-associated systemic illness.

  • Dvelopment of novel adjuvant which constructed by DNA origami technology

    Grant number:24659836  2012.4 - 2014.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    TERAO Yutaka, KAWABATA Shigetada, NAKATA Masanobu, SUMITOMO Tomoko

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    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

    Recently, pathogenic microorganisms acquired drug-resistance, and they are spreading throughout the world. Antibiotics were presented as "magic bullets" against infectious diseases in the 20th century, however, the heavy usage of antibiotics has led to the appearance of drug-resistant microorganisms. Thus, it has become difficult to treat most infantile diarrhea with basic antibiotics in the developing countries. Now, it is important to develop and improve the enteric and general immune activators on the basis of fundamental investigations. In this proposal, we focus on a CpG motif among the DNA sequence. The CpG motif is observed at high frequency in the genomes of pathogenic microorganisms. It works as an immune activator to boost production of antigen-specific immune responses. In this study, we constructed "DNA origami" immune activators being fixed the GpG motifs to the outside using M13 DNA, aiming to obtain the immunopotentiating effect.

  • Multi-dimensional analyses of a novel immune system NETs-inducer using nano live imaging technology

    Grant number:23390419  2011.4 - 2014.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    TERAO Yutaka, KAWABATA Shigetada, NAKATA Masanobu

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    Grant amount:\18980000 ( Direct Cost: \14600000 、 Indirect Cost:\4380000 )

    Recently, it was reported that neutrophils equips a novel immune system against pathogenic microorganisms. And then, it was named neutrophils extracellular traps, NETs. NETs work to trap the pathogenic bacteria and to present toward macrophages and other native neutrophils. However, they were still unknown what molecules derived from pathogens induces NETs, and what receptor on neutrophil recognize NETs-inducing molecule. Thus, we investigated to determine the molecules which induce NETs formation, and then how neutrophils recognize the NETs-inducing factor in this study. In addition, we examine the NETs-expressing neutrophils could eliminate major pathogenic bacteria, including Streptococcus pneumoniae, Streptococcus pyogenes, and Staphilococcus aures in vitro assys.

  • Analysis of virulence regulatory mechanism of group A streptococcal ncRNA

    Grant number:23592700  2011 - 2013

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    NAKATA Masanobu, KAWABATA Shigetada, TERAO Yutaka, SUMITOMO Tomoko

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    Grant amount:\5200000 ( Direct Cost: \4000000 、 Indirect Cost:\1200000 )

    Streptococcus pyogenes regulates expression of virulence factors in infection sites, and causes purulent diseases. Recently, transcriptional and translational regulations by RNA have been noted. In this study, non-coding RNA candidates were searched in Streptococcus pyogenes, and target mRNAs of non-coding RNAs were investigated using constructed mutant strains. Moreover, regarding the essential gene encoding a transcriptional regulator, an riboswitch was introduced upstream of the gene, and the function of the essential gene was analysed. When the translation rate of the gene was reduced in the mutant strain, the growth was markedly inhibited. Moreover, the mutant showed an abnormal cellular morphology and irregular superficial structure. Our results indicate that riboswitch-based translational control is useful for analysis of essential factors of Streptococcus pyogens.

  • レンサ球菌のmicroRNAがヒト組織に及ぼす病原性のオーソログ検索

    Grant number:21659423  2009 - 2010

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

    寺尾 豊, 川端 重忠, 中田 匡宣, 磯田 竜太朗

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    Grant amount:\3100000 ( Direct Cost: \3100000 )

    A群レンサ球菌の全RNAプールを作製し,ヒトのmicroRNAデータベースと相同検索を行った.その結果,3種類のヒトmicroRNA相伺体を得た,そこで.当該の3種類のA群レンサ球菌由来配列をRNA転写ベクターにそれぞれ導入し.microRNA発現ベクターを構築した(クローン#A~C).続いて,ヒト上皮細胞株へ3種類のA群レンサ球菌microRNA転写ベクターをそれぞれ導入し解析を行った
    microRNAクローン#Cの導入細胞では,上皮細胞株の基準1.0に対して300倍を超える炎症性サイトカインIL-1βの転写増強が認められた.microRNAクローン#Cは,ヒト細胞に炎症を惹起することが推察された.この結果は,A群レンサ球菌が感染後に宿主内で殺菌されても.漏出したmicroRNAが残存すれば,炎症を増悪させヒトに病原性を発揮する可能性を示唆している
    一方で,クローン#A導入細胞ではIL-17および抗菌ペプチドLL-37の転写が促進された.すなわち,Th17系の免疫応答の誘導と抗菌ペプチドによる直接的な殺菌効果が高まることが示唆された.また.microRNAクローン#B導入細胞では,TGF-β1の転写が減少した.TGF-β1はヒト細胞表層のフィブロネクチンの発現を正に制御する.多くの細菌はヒト細胞表層のフィブロネクチンを介してヒト細胞に付着・侵入することから,#B発現細胞では細菌のヒト細胞付着が減少する可能性が考えられた.そこで,A群レンサ球菌ならびに肺炎球菌の細胞付着実験を行った.その結果,A群レンサ球菌由来の#Bクローンを発現させた細胞では,A群レンサ球菌とは異なる肺炎球菌の付着低下が顕著であった.これらの知見は,A群レンサ球菌が組織内に侵入した後,他の菌種の感染を妨げA群レンサ球菌自身が効率的に組織内増殖を果たす戦略を有する可能性を示唆している

  • Searching for environmental signals sensed by group A streptococcal two-component systems

    Grant number:21791786  2009 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    NAKATA Masanobu

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    Streptococcus pyogenes (group A streptococci; GAS) is a human pathogen responsible for a wide variety of diseases that ranges from self-limiting purulent infections such as pharyngitis, tonsillitis, and impetigo to severe necrotizing fasciitis and autoimmune diseases including acute rheumatic fever and glomerulonephritis. To successfully evade host immune responses and cause such diverse diseases, GAS might acclimate to environmental changes and control the expression of a variety of genes including virulence genes. In this study, deletion mutants of genes encoding both histidine kinases and response regulators were constructed in a background of a serotype M3 GAS strain. Utilizing these mutant strains and a silkworm infection model, we revealed that several two-component systems are crucial for GAS pathogenesis. Moreover, analysis of the virulence gene expression in mutant strains under several culture conditions indicated specific environmental signals are sensed by two-component systems.

  • Functional analysis of adhesins and colonization factors produced by human pathogenic streptococci

    Grant number:20390465  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KAWABATA Shigetada, TERAO Yutaka, NAKATA Masanobu, SUMITOMO Tomoko

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    Grant amount:\19370000 ( Direct Cost: \14900000 、 Indirect Cost:\4470000 )

    The human pathogen Streptococcus pyogenes produces diverse pili depending on the serotype. In a serotype M49 S. pyogenes strain, we demonstrate that FctA is the pilus backbone protein, and FctB and Cpa, a collagen-binding adhesin, are ancillary proteins. We also found that both Cpa and FctA are trypsin-resistant T antigens. Mutagenesis assays and eukaryotic cell adherence tests revealed that FctB and housekeeping sortase SrtA contribute to the cell wall anchoring of pili, whereas Cpa functions as a pilus adhesin to human keratinocytes. Sortase C2 and putative signal peptidase LepA enzymes were crucial for polymerization of FctA. The pilus expression increased with lower temperature. The ability to form biofilms was not affected by the mutation of the pilus genes. In contrast to the M49 pili, pili of a serotype M6 S. pyogenes strain were found to be assembled from two proteins, i.e. the backbone protein T6 and ancillary protein FctX, in a manner that requires both SrtA and pilus-associated sortase SrtB. We found that T6 pili contribute to biofilm formation, but not to adherence to human keratinocytes under the condition used in this study. These data suggest the serotype-dependent pilus assembly mechanism and contribution of S. pyogenes pili to the tissue tropism.

  • Group A streptococcal proteases degrade human complements and contribute to evasion of innate immunity

    Grant number:19390463  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    TERAO Yutaka, KAWABATA Shigetada, NAKATA Masanobu

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    Grant amount:\19630000 ( Direct Cost: \15100000 、 Indirect Cost:\4530000 )

  • Analysis of the function of streptococcal heamolysin

    Grant number:19791343  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    NAKATA Masanobu

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    Grant amount:\3570000 ( Direct Cost: \3300000 、 Indirect Cost:\270000 )

  • Molecular analysis of bacterial invasion strategies and intracellular growth of pathogenic streptococci

    Grant number:18073011  2006 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research on Priority Areas

    KAWABATA Shigetada, TERAO Yutaka, NAKATA Masanobu

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    Grant amount:\93000000 ( Direct Cost: \93000000 )

    Streptococcus pyogenes causes pharyngitis, sepsis, and rheumatic fever. Cell-associated streptococcal C5a peptidase (ScpA) protects S. pyogenes from phagocytosis and has been suggested to interrupt host defenses by enzymatically cleaving complement C5a, a major factor in the accumulation of neutrophils at sites of infection. How S. pyogenes recognizes and binds to C5a, however, is unclear. We detected a C5a-binding protein in 8 M urea extracts of S. pyogenes by ligand blotting using biotinylated C5a. Searching of genome databases showed that the C5a-binding protein is identical to the streptococcal plasmin receptor (Plr), also known as streptococcal surface dehydrogenase (SDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In the present study, we identified a novel function of this multifunctional protein. We examined whether the streptococcal Plr/SDH/GAPDH inhibits the biological effects of C5a on human neutrophils. Together, these results indicate that the multifunctional protein Plr/SDH/GAPDH has additional functions that help S. pyogenes escape detection by the host immune system.

  • Protective immunity against group Astreptococcus infection following immunization with fibronectin-binding proteins

    Grant number:18390489  2006 - 2007

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    KAWABATA Shigetada, TERAO Yutaka, NEKATA Masanobu, SUMITOMO Tomoko, OKAMOTO Shigefumi

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    Grant amount:\16940000 ( Direct Cost: \15800000 、 Indirect Cost:\1140000 )

    Background. Surface-associated fibronectin (Fn) -binding proteins of group A Streptococcus pyogenes play important roles in the bacterial invasion of epithelial cells. The aim of this study was to examine the functional domain and protective antigenicity of the Fn-binding proteins FbaA and FbaB.
    Methods. To investigate the functional domain of FbaA or FbaB and their localization on S. pyogenes, a series of recombinant GST-truncated FbaA or FbaB proteins were employed for immunofluorescent microscopy, ligand blot, and Biacore analyses. Mice were immunized with the truncated proteins to determine the immunogenic domains that contribute to protection against S. pyogenes infection.
    Results. Ligand blot and Biacore analyses revealed that the FbaA fragments harboring a proline-rich repeat domain (RD), but not the N- and C-terminal regions, possessed Fn-binding activity. Immunofluorescent microscopy findings showed that the N-terminus and RD were exposed to external regions, suggesting that the RD serves as an Fn-binding element on live organisms. Specific antibodies were efficiently induced in N-terminus- and RD-immunized mice and demonstrated bactericidal activity against S. pyogenes in vitro. FbaA-immunized mice survived significantly longer as compared to the GST-immunized group following infection with M1 and M49 strains expressing FbaA. In addition, FbaB-immunized mice also survived longer than control mice after challenge with M3 strain expressing FbaB.
    Conclusion. The Fn-binding proteins, FbaA and FbaB, are potential vaccine candidates for S. pyogenes infection.

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