Molecular analysis of Shigella effector IpaH E3 ligase activity

2012 Fiscal Year Final Research Report

• 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
• Keywords: エフェクター / 赤痢菌 / ユビキチン / NF-〓B

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] 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
• [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
  • Year and Date: 20130318-0320
• [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 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