Molecular analysis of Shigella effector IpaH E3 ligase activity

• Project/Area Number: 23790472
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including Mycology)
• Research Institution: The University of Tokyo
• Principal Investigator: ASHIDA Hiroshi 東京大学, 医科学研究所, 特任助教 (10535115)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: エフェクター / 赤痢菌 / ユビキチン / NF-〓B / シグナル伝達 / 感染 / 炎症

Research Abstract

In this study, we tried to identify the mechanism of IpaH0722 in Shigella infection. IpaH0722, which has an E3 ubiquitin ligase activity, inhibits NF-〓B activity in its E3 ubiquitin ligase dependent manner. As a result, we found that IpaH0722 inhibits phagosome disruption mediated PKC-NF-〓B activation by targeting TRAF2 for ubiquitination and proteasome-dependent degradation, thereby downregulating host inflammatory responses.

Research Products

• [Journal Article] Bacteria and host interactions in the gut epithelial barrier. (2012)
  • Author(s): Ashida H, Ogawa M, Kim M, Mimuro H, &Sasakawa C.
  • Journal Title: Nature Chem Biol. Volume: 8 Pages: 36-45
• [Journal Article] The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response. (2012)
  • Author(s): Sanada T, Kim M, Mimuro H, Suzuki M, Ogawa M, Oyama A, Ashida H, Kobyashi T, Koyama T, Nagai S, Shibata Y, Gohda J, Inoue J, Mizushima T, & Sasakawa C.
  • Journal Title: Nature. Volume: 483 Pages: 623-626
• [Journal Article] A bacterial effector targets the TRAF6-NFκB pathway to modulate the acute inflammatory response to bacterial invasion of epithelial cells. (2012)
  • Author(s): Sanada T
  • Journal Title: Virulence Volume: 3 Pages: 518-521
  • Peer Reviewed
• [Journal Article] Bacteria and host interactions in the gut epithelial barrier (2012)
  • Author(s): Ashida, H., Ogawa, M., Kim, M., Mimuro, H., and Sasakawa C
  • Journal Title: Nature Chemical Biology Volume: 8 Pages: 36-45
  • Peer Reviewed
• [Journal Article] A bacterial effector deamidates Ubc13 to dampen the inflammatory response (2012)
  • Author(s): Sanada, T., Kim, M., Mimuro, H., Suzuki, M., Ogawa, M., Oyama, A., Ashida, H., Kobyashi, T., Koyama, T., Nagai, S., Shibata, Y., Gohda, J., Inoue, J., Mizushima, T., and Sasakawa, C
  • Journal Title: Nature Volume: 483 Pages: 623-626
  • Peer Reviewed
• [Journal Article] Cell death and infection: a double-edged sword for host and pathogen survival. (2011)
  • Author(s): Ashida H, Mimuro H, Ogawa M, Kobayashi T, Sanada T, Kim M, & Sasakawa C.
  • Journal Title: J Cell Biol. Volume: 195 Pages: 931-42
• [Journal Article] Shigella are versatile mucosal pathogens that circumvent the host innate immune system. (2011)
  • Author(s): Ashida H, Ogawa M, Mimuro H, Kobayashi T, Sanada T, & Sasakawa C.
  • Journal Title: Curr Opin in Immunol. Volume: 23 Pages: 448-55
• [Journal Article] Shigella deploy multiple countermeasures against host innate immune responses. (2011)
  • Author(s): Ashida H, Ogawa M, Kim M, Suzuki S, Sanada T, Punginelli C, Mimuro H, & Sasakawa C.
  • Journal Title: Curr Opin in Microbiol. Volume: 14 Pages: 16-23
• [Journal Article] BabA-mediated adherence is a potentiator of the Helicobacter pylori Type IV secretion system activity. (2011)
  • Author(s): Ishijima N, Suzuki M, Ashida H, Ichikawa Y, Kanegae Y, Saito I, Boren T, Haas R, Sasakawa C, Mimuro H.
  • Journal Title: J Biol Chem. Volume: 286 Pages: 25256-64
• [Journal Article] A tecpr1-dependent selective autophagy pathway targets bacterial pathogens. (2011)
  • Author(s): Ogawa M, Yoshikawa Y, Kobayashi T, Mimuro H, Fukumatsu M, Kiga K, Piao Z, Ashida H, Yoshida M, Kakuta S, Koyama T, Goto Y, Nagatake T, Nagai S, Kiyono H, Kawalec M, Reichhart JM, Sasakawa C.
  • Journal Title: Cell Host Microbe. Volume: 9 Pages: 376-89
• [Journal Article] Manipulation of autophagy by bacteria for their own benefit. (2011)
  • Author(s): Ogawa M, Mimuro H, Yoshikawa Y, Ashida H, & Sasakawa C.
  • Journal Title: Microbiol Immunol. Volume: 55 Pages: 459-471
  • NAID: 10031121491
• [Journal Article] Cell death and infection: a double-edged sword for host and pathogen survival (2011)
  • Author(s): Ashida, H., Mimuro, H., Ogawa, M., Kobayashi, T., Sanada, T., Kim, M., and Sasakawa, C
  • Journal Title: Journal of Cell BIology Volume: 195 Pages: 931-942
  • Peer Reviewed
• [Journal Article] Shigella are versatile mucosal pathogens that circumvent the host innate immune system (2011)
  • Author(s): Ashida, H., Ogawa, M., Mimuro, H., Kobayashi, T., Sanada, T., and Sasakawa, C
  • Journal Title: Current Opinion in Immunology Volume: 23 Pages: 448-455
  • Peer Reviewed
• [Journal Article] A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens (2011)
  • Author(s): Ogawa, M., Yoshikawa, Y., Kobayashi, T., Mimuro, H., Fukumatsu, M., Kiga, K., Piao, Z., Ashida, H.,....., Kawalec, M., Reichhart, J. M., and Sasakawa, C
  • Journal Title: Cell Host & Microbe Volume: 9 Pages: 376-389
  • Peer Reviewed
• [Journal Article] BabA-mediated adherence is a potentiator of the Helicobacter pylori type IV secretion system activity. (2011)
  • Author(s): Ishijima, N., Suzuki, M., Ashida, H., Ichikawa, Y., Kanegae, Y., Saito, I., Borén, T., Haas, R., Sasakawa, C., and Mimuro, H
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 25256-23264
  • Peer Reviewed
• [Presentation] 赤痢菌 IpaH エフェクタータンパクの機能解析" (2013)
  • Author(s): 芦田浩、笹川千尋
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉
• [Presentation] 赤痢菌IpaHエフェクタータンパクの機能解析 (2013)
  • Author(s): 芦田 浩
  • Organizer: 第86回日本細菌学会総会
  • Place of Presentation: 千葉
• [Presentation] Shigella effector protein modulates host inflammatory responses (2012)
  • Author(s): 芦田浩、笹川千尋
  • Organizer: 第85回日本細菌学会総会
  • Place of Presentation: 長崎
  • Year and Date: 2012-03-27
• [Presentation] Shigella effector protein modulates host inflammatory responses (2012)
  • Author(s): Hiroshi Ashida and Chihiro Sasakawa
  • Organizer: 第85回日本細菌学会総会(招待講演)
  • Place of Presentation: 長崎
• [Presentation] Shigella deploy multiple countermeasures against host innate immue responses.'' (2011)
  • Author(s): Ashida H and Sasakawa C.
  • Organizer: Singapore-Japan Joint Forum Emerging Concepts in Microbiology.
  • Place of Presentation: Singapore
  • Year and Date: 2011-11-16
• [Presentation] Shigella deploy multiple countermeasures against host innate immue responses (2011)
  • Author(s): Ashida H and Sasakawa C.
  • Organizer: International Union of Microbiological Societies 2011 Congress.
  • Place of Presentation: Japan
  • Year and Date: 2011-09-08
• [Presentation] Shigella deploy multiple countermeasures against host innate immue responses (2011)
  • Author(s): Hiroshi Ashida and Chihiro Sasakawa
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌
• [Presentation] Shigella deploy multiple countermeasures against host innate immue responses (2011)
  • Author(s): Hiroshi Ashida and Chihiro Sasakawa
  • Organizer: Singapore-Japan Joint Forum Emerging Concepts in Microbiology(招待講演)
  • Place of Presentation: シンガポール
• [Book] 実験医学増刊 感染・共生・生体防御システム (2012)
  • Author(s): 芦田 浩
  • Publisher: 羊土社