2007 Fiscal Year Final Research Report Summary
Analysis of the recognition mechanism of Shigella by autophagy
| Project/Area Number |
18590414
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Bacteriology (including Mycology)
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
OGAWA Michinaga The University of Tokyo, Institute of Medical Science, Assistant Professor (80361624)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Keywords | Shigella / Listeria / Autophagy / Atg5 |
|---|
| Research Abstract |
In this study, we focused on the analysis of the mechanism of autophagy induced by invasive pathogens, and planned to analyze the mechanism of autophagy induced by Shigella and another pathogens. Since, in antuohagy induced by Shigella, Atg5 play as a sensor for intracellular Shigella, we, at first, tried to find novel Atg5 interacting host proteins. By yeast-two-hybrid screening, we obtained novel protein, named Afp, as a candidate of Atg5-interacting protein. By using mammalian cells expressing GFP-LC3 and Afp-Myc, we found that Afp is localized on the surface of autophagosomes containing Shigella and group A Sreptococcus. In knock-down experiment, the reduction of the Afp expression level leads to the decrease of the autophagic activity induced by rapamycin treatment. By the result from domain analysis of Afp for the binding to Atg5, we succeeded in producing one-amino acid altered Afp mutant protein that is deficient in Atg5 binding. Next, we analyzed the autophagy inducd by Listeria monocytogenes infection in epithelial cells. L. monocytogenes is known as a intracellular motile pathogen like Shigella. As a result from screening using L. moncytogenes mutant strains, we found ActA has a pivotal role in escaping from autophagy. The recognition mechanism of autophagy for L. moncytogenesi looks different from that for Shigella and GAS. Our data suggests that L. moncytogenes is recognized as protein aggregate by host cells.
Based on our data, we may conclude that Afp is a novel protein that plays a pivotal role in autophagy induced by pathogens and mTOR inhibition, and intracellular motile pathogens such as Shigella and Listeria have a common strategy to escape from autophagy in cytoplasm of host cells.
|
-
-
-
-
-
[Journal Article] The enteropathogenic E. coli-effector EspB facilitates microvilli effacing and antiphagocytosis by inhibiting myosin function2008
Author(s)
Iizumi, Y., Sagara, H., Kabe, Y., Azuma, M., Kume, K., Ogawa, M., Nagai, T., Gillespie, P. G., Sasakawa, C. and Handa, H.
-
Journal Title
Cell Host Microbe 2
Pages: 383-392
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] 「研究成果報告書概要(和文)」より2007
Author(s)
Iwai, H., et. al.
-
Journal Title
A Bacterial Effector Targets Mad2L2, an APC In hibitor, to Modulate Host Cell Cycling. 130
Pages: 611-623
Peer Reviewed
-
[Journal Article] Bacterial Effector Targets Mad2L2, an APC Inhibitor, to Modulate Host Cell Cycling2007
Author(s)
Iwai, H., Kim, M., Yoshikawa, Y., Ashida, H., Ogawa, M., Fujita, Y., Muller, D., Kirikae, T., Jackson, P. K., Kotani, S. & Sasakawa, C. A
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
[Journal Article] Microtubule-severing activity of Shigella is pivotal for intercellular spreading2006
Author(s)
Yoshida, S., Handa, Y., Suzuki, T., Ogawa, M., Suzuki, M., Tamai, A., Abe, A., Katayama, E. and Sasakawa, C.
-
Journal Title
Science 314
Pages: 985-989
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages2006
Author(s)
Suzuki, T., Franchi, L., Toma, C., Ashida, H., Ogawa, M., Yoshikawa, Y., Mimuro, H., Inohara, N., Sasakawa, C., Nunez, G.
-
Journal Title
PLoS Pathog 3
Pages: e111
Description
「研究成果報告書概要(欧文)」より
-
-
[Presentation] 「研究成果報告書概要(欧文)」より2007
Author(s)
Yoshida, S., Handa, Y. Ogawa, M., Suzuki, M., Suzuki, T., and Sasakawa, C.
Organizer
80th annual meeting of Japanese society for bacteriology
Place of Presentation
Osaka
Year and Date
20070300
-
-
