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Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment

Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment

Nature DOI 10.1038/nature07952 (2009)
Minsoo Kim1,3, Michinaga Ogawa2,3, Yukihiro Fujita2,3, Yuko Yoshikawa2,3, Takeshi Nagai2,3, Tomohiro Koyama4, Shinya Nagai4, Anika Lange5, Reinhard Fassler5 & Chihiro Sasakawa1,2,3
1. Department of Infectious Disease Control, International Research Center for Infectious Diseases, 2. Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan 3. CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan 4. Nippon Institute for Biological Science, 9-2221-1, Shinmachi, Ome, Tokyo 198-0024, Japan 5. Department of Molecular Medicine, Max-Planck Institute of Biochemistry, D-82152, Martinsried, Germany

The rapid turnover and exfoliation of mucosal epithelial cells provides an innate defence system against bacterial infection. Nevertheless, many pathogenic bacteria, including Shigella, are able to surmount exfoliation and colonize the epithelium efficiently. Here we show that the Shigella flexneri effector OspE (consisting of OspE1 and OspE2 proteins), which is highly conserved among enteropathogenic Escherichia coli, enterohaemorrhagic E. coli, Citrobacter rodentium and Salmonella strains, reinforces host cell adherence to the basement membrane by interacting with integrin-linked kinase (ILK). The number of focal adhesions was augmented along with membrane fraction ILK by ILK–OspE binding. The interaction between ILK and OspE increased cell surface levels of beta1 integrin and suppressed phosphorylation of focal adhesion kinase and paxillin, which are required for rapid turnover of focal adhesion in cell motility. Nocodazole-washout-induced focal adhesion disassembly was blocked by expression of OspE. Polarized epithelial cells infected with a Shigella mutant lacking the ospE gene underwent more rapid cell detachment than cells infected with wild-type Shigella. Infection of guinea pig colons with Shigella corroborated the pivotal role of the OspE–ILK interaction in suppressing epithelial detachment, increasing bacterial cell-to-cell spreading, and promoting bacterial colonization. These results indicate that Shigella sustain their infectious foothold by using special tactics to prevent detachment of infected cells.