Inhibitory effect of gut commensals against pathogenic organisms

• Project/Area Number: 23590511
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Kagawa University
• Principal Investigator: KUWAHARA Tomomi 香川大学, 医学部, 教授 (60263810)
• Co-Investigator(Kenkyū-buntansha): NAKAYAMA Haruyuki 香川大学, 医学部, 助教 (80294669)
• Co-Investigator(Renkei-kenkyūsha): ICHIMURA Minoru
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腸内細菌 / 毒素 / 多糖 / 細胞毒性 / バクテロイデス / 抗菌薬 / 下痢症 / 溶菌 / Bacteroides / Clostridium difficile / 偽膜性腸炎 / Toxin B / トランスポゾン / 莢膜多糖 / 自己溶菌 / 菌交代症 / 毒素産生 / 偽膜性大腸炎

Research Abstract

Human intestinal symbiont, Bacteroides thetaiotaomicron (BT) showed inhibitory effect in its culture supernatant against the cytotoxicity of Clostridium difficile (CD). Screening of Tn4351 insertion mutant library of BT identified the mutants that lost the inhibitory effect on CD cytotoxicity. In these mutants, Tn4351 was inserted into the genes for polysaccharide transport or capsular polysaccharide biosynthesis. These results indicate that the polysaccharides produced by BT play roles in the inhibition of CD cytotoxicity.

Research Products

• [Journal Article] X-ray structure of a novel endolysin encoded by episomal phage phiSM101 of Clostridium perfringens (2014)
  • Author(s): Tamai E, Yoshida H, Sekiya H, Nariya H, Miyata S, Okabe A, Kuwahara T, Miaki J, Kamitori S
  • Journal Title: Mol. Microbiol. Volume: 92 Pages: 326-337
  • Peer Reviewed
• [Journal Article] Inhibition by caffeic acid of the influenza A virus multiplication in vitro (2014)
  • Author(s): Utsunomiya H, Ichinose M, Ikeda K, Uozaki M, Morishita J, Kuwahara T, Koyama AH, Yamasaki H
  • Journal Title: Int. J. Mol..Med. Volume: (in press)
  • Peer Reviewed
• [Journal Article] X-ray structure of a novel endolysin encoded by episomal phage phiSM101 of Clostridium perfringens (2014)
  • Author(s): Tamai, E., Yoshida, H., Sekiya, H., Nariya, H., Miyata, S., Okabe, A., Kuwahara, T., Maki, J. & Kamitori, S
  • Journal Title: Mol. Microbiol Volume: 92 Issue: 2 Pages: 326-337
  • DOI: 10.1111/mmi.12559
  • Peer Reviewed
• [Journal Article] Effect of Kampo medicine"Dai-kenchu-to"on microbiome in the intestine of the rats with fast stress (2013)
  • Author(s): Yoshikawa K, Shimada M, Kuwahara T, Hirakawa H, Kurita N, Sato H, Utsunomiya T, Iwata T, Miyatani T, Higashijima J, Kashihara H, Takasu C, Matsumoto N, Nakayama-Imaohji H
  • Journal Title: J. Med. Invest. Volume: 60 Pages: 221-227
  • NAID: 130004822686
  • Peer Reviewed
• [Journal Article] Infectious conjunctivitis caused by Pseudomonas aeruginosa isolated from a bathroom (2013)
  • Author(s): Eguchi H, Miyamoto T, Kuwahara T, Mitamura S, Miamura Y
  • Journal Title: BMC Res Notes Volume: 6 Pages: 245-245
  • NAID: 120006864092
  • Peer Reviewed
• [Journal Article] Mariner-based transposon mutagenesis for Bacteroides species (2013)
  • Author(s): Ichimura M, Uchida K, Nakayama-Imaohji H, Hirakawa H, Tada T, Morita H, Yasutomo K, Okazaki K, Kuwahara T
  • Journal Title: J Basic Microbiol Volume: (in press)
• [Journal Article] PhoB regulates the survival of Bacteroides fragilis in peritoneal abscesses (2013)
  • Author(s): Wakimoto S, Nakayama-Imaohji H, Ichimura M, Morita H, Hirakawa H, Hayashi T, Yasutomo K, Kuwahara T
  • Journal Title: PLoS One Volume: 8
• [Journal Article] Effect of Kampo medicine “Dai-kenchu-to” on microbiome in the intestine of the rats with fast stress. (2013)
  • Author(s): Yoshikawa K, Shimada M, Kuwahara T, Hirakawa H, Kurita N, Sato H, Utsunomiya T, Iwata T, Miyatani T, Higashijima J, Kashihara H, Takasu C, Matsumoto N, Nakayama-Imaohji H.
  • Journal Title: J. Med. Invest. Volume: 60 Pages: 221-227
  • NAID: 130004822686
  • Peer Reviewed
• [Journal Article] Infectious conjunctivitis caused by Pseudomonas aeruginosa isolated from a bathroom. (2013)
  • Author(s): Eguchi H, Miyamoto T, Kuwahara T, Mitamura S, Miamura Y.
  • Journal Title: BMC Res Notes. Volume: 6 Pages: 245-245
  • NAID: 120006864092
  • Peer Reviewed
• [Journal Article] PhoB regulates the survival of Bacteroides fragilis in peritoneal abscesse. (2013)
  • Author(s): Wakimoto S, et al.
  • Journal Title: PLoS One Volume: 8 Issue: 1 Pages: e53829-e53829
  • DOI: 10.1371/journal.pone.0053829
  • Peer Reviewed
• [Journal Article] Evaluation method for the potential functionome harbored in the genome and metagenome (2012)
  • Author(s): Takami H, Taniguchi T, Moriya Y, Kuwahara T, Kanehisa M, Goto S
  • Journal Title: BMC Genomics Volume: 13 Pages: 699-699
  • Peer Reviewed
• [Journal Article] Effect of indole-3-carbinol and phenethyl isothiocyanate on bile and pancreatic juice excretion in rats (2012)
  • Author(s): Ishibashi H, Kuwahara T, Nakayama-Imaohji H, Ohnishi Y, Mori H, Shimada M
  • Journal Title: J Med Invest Volume: 59 Pages: 246-252
  • NAID: 130004822672
  • Peer Reviewed
• [Journal Article] Reduced diversity and imbalance of fecal microbiota in patients with ulcerative colitis (2012)
  • Author(s): Nemoto H, Kataoka K, Ishikawa H, Ikata K, Arimochi H, Iwasaki T, Ohnishi Y, Kuwahara T, Yasutomo K
  • Journal Title: Dig Dis Sci Volume: 57 Pages: 2955-2964
  • Peer Reviewed
• [Journal Article] Characterization of a gene cluster for sialoglycoconjugate utilization in Bacteroides fragilis (2012)
  • Author(s): Nakayama-Imaohji H, Ichimura M, Iwasa T, Okada N, Ohnishi Y, Kuwahara, T
  • Journal Title: J Med Invest. Volume: 59 Pages: 79-94
  • NAID: 130004465274
  • Peer Reviewed
• [Journal Article] Evaluation method for the potential functionome harbored in the genome and metagenome. (2012)
  • Author(s): Takami H, Taniguchi T, Moriya Y, Kuwahara T, Kanehisa M, Goto S.
  • Journal Title: BMC Genomics Volume: 13 Issue: 1 Pages: 699-699
  • DOI: 10.1186/1471-2164-13-699
  • Peer Reviewed
• [Journal Article] Reduced diversity and imbalance of fecal microbiota in patients with ulcerative colitis (2012)
  • Author(s): Nemoto H, Kataoka K, Ishikawa H, Ikata K, Arimochi H, Iwasaki T, Ohnishi Y, Kuwahara T, Yasutomo K
  • Journal Title: Digestive Diseases and Science Volume: Vol 57 Issue: 11 Pages: 2955-2964
  • DOI: 10.1007/s10620-012-2236-y
  • Peer Reviewed
• [Journal Article] Characterization of a gene cluster for sialoglycoconjugate utilization in Bacteroides fragilis. (2012)
  • Author(s): Nakayama-Imaohji H, Ichimura M, Iwasa T, Okada N, Ohnishi Y, Kuwahara, T
  • Journal Title: J Med Invest Volume: 59 Pages: 79-94
  • NAID: 130004465274
  • Peer Reviewed
• [Journal Article] Development and characterization of a xylose-inducible gene expression system for Clostridium perfringens (2011)
  • Author(s): Nariya H, Miyata S, Kuwahara T, Okabe A
  • Journal Title: Appl Environ Microbiol Volume: 77 Pages: 8439-8441
  • Peer Reviewed
• [Journal Article] The lifestyle of the segmented filamentous bacterium : a non-culturable gut-associated immunostimulating microbe inferred by whole-genome sequencing (2011)
  • Author(s): Kuwahara T, Ogura Y, Oshima K, Kurokawa K, Ooka T, Hirakawa H, Itoh T, Nakayama-Imaohji H, Ichimura M, Itoh K, Ishifune C, Maekawa Y, Yasutomo K, Hattori M, Hayashi T
  • Journal Title: DNA Res Volume: 18 Pages: 291-303
  • Peer Reviewed
• [Journal Article] Anti-microbial and therapeutic effects of modified Burow's solution on refractory otorrhea (2011)
  • Author(s): Jinnouchi O, Kuwahara T, Ishida S, Okano Y, Kasei Y, Kunitomo K, Takeda N
  • Journal Title: Auris Nasus Larynx Volume: 39 Pages: 374-377
  • Peer Reviewed
• [Journal Article] Blockade of Th1 chemokine receptors ameliorates pulmonary granulomatosis in mice (2011)
  • Author(s): Kishi J, Nishioka Y, Kuwahara T, Kakiuchi S, Azuma M, Aono Y, Makino H, Kinoshita K, Kishi M, Batmunkh R, Uehara H, Izumi K, Sone S
  • Journal Title: Eur Respir J Volume: 38 Pages: 415-424
  • Peer Reviewed
• [Journal Article] Effects of fermented brown rice on the intestinal environments in healthy adult (2011)
  • Author(s): Nemoto H, Ikata K, Arimochi H, Iwasaki T, Ohnishi Y, Kuwahara T, Kataoka K
  • Journal Title: J Med Invest Volume: 58 Pages: 235-245
  • NAID: 130004822662
  • Peer Reviewed
• [Journal Article] Development and characterization of a xylose-inducible gene expression system for Clostridium perfringens. (2011)
  • Author(s): Nariya H, Miyata S, Kuwahara T, Okabe A
  • Journal Title: Appl Environ Microbiol Volume: 77 Pages: 8439-8441
  • Peer Reviewed
• [Journal Article] The Lifestyle of the Segmented Filamentous Bacterium : A Non-Culturable Gut-Associated Immunostimulating Microbe Inferred by Whole-Genome Sequencing (2011)
  • Author(s): Kuwahara T, et al
  • Journal Title: DNA Research Volume: 18 Issue: 4 Pages: 291-303
  • DOI: 10.1093/dnares/dsr022
  • Peer Reviewed
• [Presentation] マウス腸内難培養菌の胞子精製と発芽誘導 (2014)
  • Author(s): 鈴木基生、今大路治之、堀内功典、桑原知己
  • Organizer: 第87回日本細菌学会総会、ワークショップ「難培養を如何に克服するか」
  • Place of Presentation: 東京
• [Presentation] Raoultella ornithinolyticaにおけるhistamine産生は酸素ストレス耐性に関与する (2014)
  • Author(s): 今大路治之、大岡唯祐、後藤恭宏、成谷宏文、堀内功典、鈴木基生、岡崎勝一郎、林哲也、桑原知己
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
• [Presentation] Porphyromonas gingivalisにおける電気穿孔法に適した新規プラスミドベクターの構築 (2014)
  • Author(s): 田川淳平、井上哲圭、佐藤啓子、内藤真理子、中山真彰、中山浩次、桑原知己、大原直也
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
• [Presentation] Novel cloning system of large exogenous DNA as artificial chromosome in Clostridium perfringens (2014)
  • Author(s): 成谷宏文、今大路治之、宮田茂、桑原知己
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
• [Presentation] O1エルトール型コレラ菌のレトロン-Vc95内機能未知遺伝子orf205の機能解析 (2014)
  • Author(s): 島本敏、成谷宏文、桑原知己、島本整
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
• [Presentation] "亜塩素酸水"の殺微生物効果について (2014)
  • Author(s): 堀内功典、今大路治之、鈴木基生、桑原知己
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
• [Presentation] マウス腸内難培養菌の胞子精製と発芽誘導 (2014)
  • Author(s): 鈴木基生、今大路治之、堀内功典、桑原知己
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Novel cloning system of large exogenous DNA as artificial chromosome in Clostridium perfringens. (2014)
  • Author(s): 成谷宏文、今大路治之、宮田茂、桑原知己
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
• [Presentation] “亜塩素酸水”の殺微生物効果について (2014)
  • Author(s): 堀内功典、今大路治之、鈴木基生、桑原知己
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
• [Presentation] 腸管内における宿主微生物間相互作用に関わる分子の検索 (2013)
  • Author(s): 桑原知己
  • Organizer: 第86回日本細菌学会総会、ワークショップ「細菌間および細菌宿主間の相互作用」
  • Place of Presentation: 千葉
• [Presentation] 腸管内における宿主微生物間相互作用に関わる分子の検索 (2013)
  • Author(s): 桑原知己
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉
• [Presentation] 腸管内常在菌がClostridium difficileの病原性に与える影響 (2012)
  • Author(s): 今大路治之、堀内功典、桑原知己
  • Organizer: 第83回日本感染症学会西日本地方会
  • Place of Presentation: 大阪
• [Presentation] 腸管内常在菌によるClostridium difficileの病原性抑制機構 (2012)
  • Author(s): 市村穣、今大路治之、内田景子、安友康二、桑原知己
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Bacteroides thetaiotaomicronにおけるマリナートランスポゾン挿入変異ライブラリーの開発 (2012)
  • Author(s): 内田景子、市村穣、今大路治之、岡崎勝一郎、桑原知己
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Human gut microbe secrete the molecules that inhibit the toxin synthesis of Clostridium difficile. (2012)
  • Author(s): Ichimura M, Nakayama-Imaohji H, Kuwahara T
  • Organizer: The 11th Korea-Japan International Symposium onMicrobiology
  • Place of Presentation: 扶余 （韓国）
• [Presentation] ゲノムからみたマウス腸内セグメント細菌の生態 (2011)
  • Author(s): 桑原知巳
  • Organizer: ゲノム微生物学会ワークショップ
  • Place of Presentation: 仙台
• [Presentation] Efficient electrotransformation strategies of Bacteroides fragilis (2011)
  • Author(s): Ichimura M, Kuwahara T, Nakayama-Imaohji H, Yasutomo K
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
• [Presentation] Dynamic regulation of the DNA inversions in susC/susD genes clusters by a single tyrosine site-specific recombinase in Bacteroides fragilis (2011)
  • Author(s): Nakayama-Imaohji H, Kuwahara T, Ichimura M, Yasutomo K
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo