title: The type III system-secreted effector EspZ localizes to host mitochondria and interacts with the translocase of inner mitochondrial membrane 17b.
abstract: Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively) are attaching and effacing (A/E) bacterial pathogens that cause severe diarrheal disease worldwide. To cause disease, A/E pathogens require a type III secretion system, which facilitates transport of bacterial effector proteins directly into infected host cells. One of these effector proteins translocated by the type III secretion system, EspZ, is essential for A/E pathogen infection and functions to prevent rapid death of EPEC-infected cells. We further investigated the mechanism of EspZ-mediated protection of infected host cells and found that a severe decrease in host mitochondrial membrane potential (Δψ(m)) occurs concurrently with host cell lysis during infection with EPEC lacking EspZ (ΔespZ). It was also demonstrated that EspZ localizes to host cell mitochondria and interacts with the translocase of inner mitochondrial membrane 17b (TIM17b). In addition, host cell cytotoxicity was exacerbated in the absence of TIM17b during wild-type (WT) EPEC infection. The findings of this study together provide the first evidence that EspZ localizes to host mitochondria and that TIM17b contributes to protection against rapid cell death during EPEC infection.
authors.affiliation: Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Shames
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Croxen
authors.forename: Wanyin
authors.initials: W
authors.lastname: Deng
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D002460:Cell Line; D004926:Escherichia coli / Q000145:classification / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D029968:Escherichia coli Proteins; C569164:EspZ protein, E coli; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D034741:RNA, Small Interfering; C569163:TIMM17B protein, human