The pathogenic E. coli type III effector EspZ interacts with host CD98 and facilitates host cell prosurvival signalling |
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| Authors: | Stephanie R Shames Wanyin Deng Julian A Guttman Carmen L De Hoog Yuling Li Philip R Hardwidge Ho Pan Sham Bruce A Vallance Leonard J Foster B Brett Finlay |
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| Institution: | 1. Michael Smith Laboratories,;2. Department of Microbiology and Immunology,;3. Present addresses: Department of Biological Science, Simon Fraser University, Burnaby, BC, Canada V5A 1S6;4. Centre for High‐Throughput Biology and Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada V6T 1Z4;5. Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA.;6. Division of Gastroenterology, B.C Children's Hospital University of British Columbia, Vancouver, BC, Canada V6H 3V4.;7. Centre for High‐Throughput Biology and;8. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z4. |
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| 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 ΔespZ 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. |
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