title: Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment.
abstract: 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 1 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.
authors.affiliation: Department of Infectious Disease Control, International Research Center for Infectious Diseases, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Kim
authors.forename: Michinaga
authors.initials: M
authors.lastname: Ogawa
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Fujita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Koyama
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagai
authors.forename: Anika
authors.initials: A
authors.lastname: Lange
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sasakawa
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity; D003106:Colon / Q000382:microbiology; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology; D022001:Focal Adhesions / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012763:Shigella flexneri / Q000472:pathogenicity / Q000502:physiology*; D037521:Virulence Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D001425:Bacterial Outer Membrane Proteins; D019012:Integrin beta1; D015739:Nocodazole; D017346:Protein Serine-Threonine Kinases; D037521:Virulence Factors; D000099200:Scaffold Protein ILK