title: The pathogenic E. coli type III effector EspZ interacts with host CD98 and facilitates host cell prosurvival signalling.
abstract: Enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC respectively) are diarrhoeal pathogens that cause the formation of attaching and effacing (A/E) lesions on infected host cells. These pathogens encode a type III secretion system (T3SS) used to inject effector proteins directly into host cells, an essential requirement for virulence. In this study, we identified a function for the type III secreted effector EspZ. Infection with EPEC DeltaespZ caused increased cytotoxicity in HeLa and MDCK cells compared with wild-type EPEC, and expressing espZ in cells abrogated this effect. Using yeast two-hybrid, proteomics, immunofluorescence and co-immunoprecipitation, it was demonstrated that EspZ interacts with the host protein CD98, which contributes to protection against EPEC-mediated cytotoxicity. EspZ enhanced phosphorylation of focal adhesion kinase (FAK) and AKT during infection with EPEC, but CD98 only appeared to facilitate FAK phosphorylation. This study provides evidence that EspZ and CD98 promote host cell survival mechanisms involving FAK during A/E pathogen infection.
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Shames
authors.forename: Wanyin
authors.initials: W
authors.lastname: Deng
authors.forename: Julian A
authors.initials: JA
authors.lastname: Guttman
authors.forename: Carmen L
authors.initials: CL
authors.lastname: de Hoog
authors.forename: Yuling
authors.initials: Y
authors.lastname: Li
authors.forename: Philip R
authors.initials: PR
authors.lastname: Hardwidge
authors.forename: Ho Pan
authors.initials: HP
authors.lastname: Sham
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vallance
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D000818:Animals; D058947:Bacterial Secretion Systems; D002460:Cell Line; D004285:Dogs; D054308:Enteropathogenic Escherichia coli / Q000378:metabolism* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000502:physiology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014774:Virulence
chemical_list: D058947:Bacterial Secretion Systems; D029968:Escherichia coli Proteins; D027261:Fusion Regulatory Protein-1; C103307:SepZ protein, E coli; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt