Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Published Online December 2, 2004
Science DOI: 10.1126/science.1106036

Reports

Submitted on October 5, 2004
Accepted on November 19, 2004

Escape of Intracellular Shigella from Autophagy

Michinaga Ogawa 1, Tamotsu Yoshimori 2, Toshihiko Suzuki 3, Hiroshi Sagara 4, Noboru Mizushima 5, Chihiro Sasakawa 6*

1 Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
2 Department of Cell Genetics, National Institute of Genetics, 1111, Yata, Mishima, Shizuoka 411-8540, Japan; CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
3 Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; PRESTO, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
4 Department of Fine Morphology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
5 Department of Bioregulation and Metabolism, Tokyo Metropolitan Institute of Medical Science, 3-18-22, Hon-komagome, Bunkyo-ku, Tokyo 113-8613, Japan; PRESTO, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
6 Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.

* To whom correspondence should be addressed.
Chihiro Sasakawa , E-mail: sasakawa{at}ims.u-tokyo.ac.jp

The degradation of undesirable cellular components or organelles, including invading microbes, by autophagy is crucial for cell survival. Here, Shigella, an invasive bacteria, was found to be able to escape autophagy by secreting IcsB via the type III secretion system. Mutant bacteria lacking IcsB were trapped by autophagy during multiplication within the host cells. IcsB did not directly inhibit autophagy. Rather, Shigella VirG, a protein required for intracellular actin-based motility, induced autophagy by binding to the autophagy protein, Atg5. In non-mutant Shigella, this binding is competitively inhibited by IcsB binding to VirG.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Molecular basis of canonical and bactericidal autophagy.
T. Noda and T. Yoshimori (2009)
Int. Immunol. 21, 1199-1204
   Abstract »    Full Text »    PDF »
The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway.
Y. T. Zheng, S. Shahnazari, A. Brech, T. Lamark, T. Johansen, and J. H. Brumell (2009)
J. Immunol. 183, 5909-5916
   Abstract »    Full Text »    PDF »
Peroxisome Size Provides Insights into the Function of Autophagy-related Proteins.
T. Y. Nazarko, J.-C. Farre, and S. Subramani (2009)
Mol. Biol. Cell 20, 3828-3839
   Abstract »    Full Text »    PDF »
The autophagy machinery is required to initiate hepatitis C virus replication.
M. Dreux, P. Gastaminza, S. F. Wieland, and F. V. Chisari (2009)
PNAS 106, 14046-14051
   Abstract »    Full Text »    PDF »
Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages.
G. B. Kyei, C. Dinkins, A. S. Davis, E. Roberts, S. B. Singh, C. Dong, L. Wu, E. Kominami, T. Ueno, A. Yamamoto, et al. (2009)
J. Cell Biol. 186, 255-268
   Abstract »    Full Text »    PDF »
A Novel Hybrid Yeast-Human Network Analysis Reveals an Essential Role for FNBP1L in Antibacterial Autophagy.
A. Huett, A. Ng, Z. Cao, P. Kuballa, M. Komatsu, M. J. Daly, D. K. Podolsky, and R. J. Xavier (2009)
J. Immunol. 182, 4917-4930
   Abstract »    Full Text »    PDF »
ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery.
C. H. Jung, C. B. Jun, S.-H. Ro, Y.-M. Kim, N. M. Otto, J. Cao, M. Kundu, and D.-H. Kim (2009)
Mol. Biol. Cell 20, 1992-2003
   Abstract »    Full Text »    PDF »
Host Cell Autophagy Is Induced by Toxoplasma gondii and Contributes to Parasite Growth.
Y. Wang, L. M. Weiss, and A. Orlofsky (2009)
J. Biol. Chem. 284, 1694-1701
   Abstract »    Full Text »    PDF »
Autophagosome Supports Coxsackievirus B3 Replication in Host Cells.
J. Wong, J. Zhang, X. Si, G. Gao, I. Mao, B. M. McManus, and H. Luo (2008)
J. Virol. 82, 9143-9153
   Abstract »    Full Text »    PDF »
Vibrio parahaemolyticus orchestrates a multifaceted host cell infection by induction of autophagy, cell rounding, and then cell lysis.
D. L. Burdette, M. L. Yarbrough, A. Orvedahl, C. J. Gilpin, and K. Orth (2008)
PNAS 105, 12497-12502
   Abstract »    Full Text »    PDF »
Host-Directed Drug Targeting of Factors Hijacked by Pathogens.
A. Schwegmann and F. Brombacher (2008)
Science Signaling 1, re8
   Abstract »    Full Text »    PDF »
Mutagenesis of the Shigella flexneri Autotransporter IcsA Reveals Novel Functional Regions Involved in IcsA Biogenesis and Recruitment of Host Neural Wiscott-Aldrich Syndrome Protein.
K. L. May and R. Morona (2008)
J. Bacteriol. 190, 4666-4676
   Abstract »    Full Text »    PDF »
Critical Role for Transcription Factor C/EBP-{beta} in Regulating the Expression of Death-Associated Protein Kinase 1.
P. Gade, S. K. Roy, H. Li, S. C. Nallar, and D. V. Kalvakolanu (2008)
Mol. Cell. Biol. 28, 2528-2548
   Abstract »    Full Text »    PDF »
Molecular Pathogenesis of Shigella spp.: Controlling Host Cell Signaling, Invasion, and Death by Type III Secretion.
G. N. Schroeder and H. Hilbi (2008)
Clin. Microbiol. Rev. 21, 134-156
   Abstract »    Full Text »    PDF »
Analysis of the Role of Autophagy in Replication of Herpes Simplex Virus in Cell Culture.
D. E. Alexander, S. L. Ward, N. Mizushima, B. Levine, and D. A. Leib (2007)
J. Virol. 81, 12128-12134
   Abstract »    Full Text »    PDF »
Autophagy: process and function.
N. Mizushima (2007)
Genes & Dev. 21, 2861-2873
   Abstract »    Full Text »    PDF »
Type III Secretion Systems and Disease.
B. Coburn, I. Sekirov, and B. B. Finlay (2007)
Clin. Microbiol. Rev. 20, 535-549
   Abstract »    Full Text »    PDF »
siRNA Screening of the Kinome Identifies ULK1 as a Multidomain Modulator of Autophagy.
E. Y. W. Chan, S. Kir, and S. A. Tooze (2007)
J. Biol. Chem. 282, 25464-25474
   Abstract »    Full Text »    PDF »
The Atg5 Atg12 conjugate associates with innate antiviral immune responses.
N. Jounai, F. Takeshita, K. Kobiyama, A. Sawano, A. Miyawaki, K.-Q. Xin, K. J. Ishii, T. Kawai, S. Akira, K. Suzuki, et al. (2007)
PNAS 104, 14050-14055
   Abstract »    Full Text »    PDF »
Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy.
S. Alonso, K. Pethe, D. G. Russell, and G. E. Purdy (2007)
PNAS 104, 6031-6036
   Abstract »    Full Text »    PDF »
The Crystal Structure of Atg3, an Autophagy-related Ubiquitin Carrier Protein (E2) Enzyme that Mediates Atg8 Lipidation.
Y. Yamada, N. N. Suzuki, T. Hanada, Y. Ichimura, H. Kumeta, Y. Fujioka, Y. Ohsumi, and F. Inagaki (2007)
J. Biol. Chem. 282, 8036-8043
   Abstract »    Full Text »    PDF »
Structure of Atg5{middle dot}Atg16, a Complex Essential for Autophagy.
M. Matsushita, N. N. Suzuki, K. Obara, Y. Fujioka, Y. Ohsumi, and F. Inagaki (2007)
J. Biol. Chem. 282, 6763-6772
   Abstract »    Full Text »    PDF »
Atg19 Mediates a Dual Interaction Cargo Sorting Mechanism in Selective Autophagy.
C.-Y. Chang and W.-P. Huang (2007)
Mol. Biol. Cell 18, 919-929
   Abstract »    Full Text »    PDF »
Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and {alpha}-Synuclein.
S. Sarkar, J. E. Davies, Z. Huang, A. Tunnacliffe, and D. C. Rubinsztein (2007)
J. Biol. Chem. 282, 5641-5652
   Abstract »    Full Text »    PDF »
Protective role of autophagy against Vibrio cholerae cytolysin, a pore-forming toxin from V. cholerae.
M. G. Gutierrez, H. A. Saka, I. Chinen, F. C. M. Zoppino, T. Yoshimori, J. L. Bocco, and M. I. Colombo (2007)
PNAS 104, 1829-1834
   Abstract »    Full Text »    PDF »
The Vacuolar Transporter Chaperone (VTC) Complex Is Required for Microautophagy.
A. Uttenweiler, H. Schwarz, H. Neumann, and A. Mayer (2007)
Mol. Biol. Cell 18, 166-175
   Abstract »    Full Text »    PDF »
Autophagy: Eating for Good Health.
M. S. Swanson (2006)
J. Immunol. 177, 4945-4951
   Abstract »    Full Text »    PDF »
Autophagy Is Induced in CD4+ T Cells and Important for the Growth Factor-Withdrawal Cell Death.
C. Li, E. Capan, Y. Zhao, J. Zhao, D. Stolz, S. C. Watkins, S. Jin, and B. Lu (2006)
J. Immunol. 177, 5163-5168
   Abstract »    Full Text »    PDF »
High Vaccine Efficacy against Shigellosis of Recombinant Noninvasive Shigella Mutant That Expresses Yersinia Invasin.
T. Suzuki, Y. Yoshikawa, H. Ashida, H. Iwai, T. Toyotome, H. Matsui, and C. Sasakawa (2006)
J. Immunol. 177, 4709-4717
   Abstract »    Full Text »    PDF »
From the Cover: Autophagy-mediated reentry of Francisella tularensis into the endocytic compartment after cytoplasmic replication.
C. Checroun, T. D. Wehrly, E. R. Fischer, S. F. Hayes, and J. Celli (2006)
PNAS 103, 14578-14583
   Abstract »    Full Text »    PDF »
Human IRGM Induces Autophagy to Eliminate Intracellular Mycobacteria.
S. B. Singh, A. S. Davis, G. A. Taylor, and V. Deretic (2006)
Science 313, 1438-1441
   Abstract »    Full Text »    PDF »
Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages.
Y. M. Ling, M. H. Shaw, C. Ayala, I. Coppens, G. A. Taylor, D. J.P. Ferguson, and G. S. Yap (2006)
J. Exp. Med. 203, 2063-2071
   Abstract »    Full Text »    PDF »
Functional Analysis of the ATG8 Homologue Aoatg8 and Role of Autophagy in Differentiation and Germination in Aspergillus oryzae..
T. Kikuma, M. Ohneda, M. Arioka, and K. Kitamoto (2006)
Eukaryot. Cell 5, 1328-1336
   Abstract »    Full Text »    PDF »
Autophagy in Innate Immunity against Intracellular Bacteria.
A. Amano, I. Nakagawa, and T. Yoshimori (2006)
J. Biochem. 140, 161-166
   Abstract »    Full Text »    PDF »
OspE2 of Shigella sonnei Is Required for the Maintenance of Cell Architecture of Bacterium-Infected Cells..
M. Miura, J. Terajima, H. Izumiya, J. Mitobe, T. Komano, and H. Watanabe (2006)
Infect. Immun. 74, 2587-2595
   Abstract »    Full Text »    PDF »
BopC Is a Novel Type III Effector Secreted by Bordetella bronchiseptica and Has a Critical Role in Type III-dependent Necrotic Cell Death.
A. Kuwae, T. Matsuzawa, N. Ishikawa, H. Abe, T. Nonaka, H. Fukuda, S. Imajoh-Ohmi, and A. Abe (2006)
J. Biol. Chem. 281, 6589-6600
   Abstract »    Full Text »    PDF »
Genome-Wide RNAi Screen for Host Factors Required for Intracellular Bacterial Infection.
H. Agaisse, L. S. Burrack, J. A. Philips, E. J. Rubin, N. Perrimon, and D. E. Higgins (2005)
Science 309, 1248-1251
   Abstract »    Full Text »    PDF »
IpgB1 Is a Novel Shigella Effector Protein Involved in Bacterial Invasion of Host Cells: ITS ACTIVITY TO PROMOTE MEMBRANE RUFFLING VIA RAC1 AND CDC42 ACTIVATION.
K. Ohya, Y. Handa, M. Ogawa, M. Suzuki, and C. Sasakawa (2005)
J. Biol. Chem. 280, 24022-24034
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)