IcsA is a Shigella flexneri adhesin regulated by the type III secretion system and required for pathogenesis.
Following contact with the epithelium, the enteric intracellular bacterial pathogen Shigella flexneri invades epithelial cells and escapes intracellular phagosomal destruction using its type III secretion system (T3SS). The bacterium replicates within the host cell cytosol and spreads between cells using actin-based motility, which is mediated by the virulence factor IcsA (VirG). Whereas S. flexneri invasion is well characterized, adhesion mechanisms of the bacterium remain elusive. We found that IcsA also functions as an adhesin that is both necessary and sufficient to promote contact with host cells. As adhesion can be beneficial or deleterious depending on the host cell type, S. flexneri regulates IcsA-dependent adhesion. Activation of the T3SS in response to the bile salt deoxycholate triggers IcsA-dependent adhesion and enhances pathogen invasion. IcsA-dependent adhesion contributes to virulence in a mouse model of shigellosis, underscoring the importance of this adhesin to S. flexneri pathogenesis.
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin 13353, Germany.
Anna
A
Brotcke Zumsteg
Microscopy Core Facility, Max Planck Institute for Infection Biology, Berlin 13353, Germany.
Christian
C
Goosmann
Microscopy Core Facility, Max Planck Institute for Infection Biology, Berlin 13353, Germany.
Volker
V
Brinkmann
School of Molecular and Biomedical Science, University of Adelaide, Adelaide 5000, South Australia, Australia.
Renato
R
Morona
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin 13353, Germany. Electronic address: zychlinsky@mpiib-berlin.mpg.de.
Arturo
A
Zychlinsky
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001422:Bacterial Adhesion / Q000187:drug effects / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000494:pharmacology; D004405:Dysentery, Bacillary / Q000382:microbiology / Q000473:pathology; D004847:Epithelial Cells / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D012763:Shigella flexneri / Q000235:genetics / Q000472:pathogenicity*; D014157:Transcription Factors / Q000378:metabolism*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D002756:Cholagogues and Choleretics; D004268:DNA-Binding Proteins; C095770:IpaD protein, Shigella flexneri; D014157:Transcription Factors; C058483:virG protein, Shigella flexneri; D003840:Deoxycholic Acid; C087447:ipaB protein, Shigella