EspZ of Enteropathogenic and Enterohemorrhagic Escherichia coli Regulates Type III Secretion System Protein Translocation

Title: EspZ of Enteropathogenic and Enterohemorrhagic Escherichia coli Regulates Type III Secretion System Protein Translocation
Author(s): Berger, CN
Crepin, VF
Baruch, K
Mousnier, A
Rosenshine, I
Frankel, G
Item Type: Journal Article
Abstract: Translocation of effector proteins via a type III secretion system (T3SS) is a widespread infection strategy among Gram-negative bacterial pathogens. Each pathogen translocates a particular set of effectors that subvert cell signaling in a way that suits its particular infection cycle. However, as effector unbalance might lead to cytotoxicity, the pathogens must employ mechanisms that regulate the intracellular effector concentration. We present evidence that the effector EspZ controls T3SS effector translocation from enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli. Consistently, an EPEC espZ mutant is highly cytotoxic. Following ectopic expression, we found that EspZ inhibited the formation of actin pedestals as it blocked the translocation of Tir, as well as other effectors, including Map and EspF. Moreover, during infection EspZ inhibited effector translocation following superinfection. Importantly, while EspZ of EHEC O157:H7 had a universal “translocation stop” activity, EspZ of EPEC inhibited effector translocation from typical EPEC strains but not from EHEC O157:H7 or its progenitor, atypical EPEC O55:H7. We found that the N and C termini of EspZ, which contains two transmembrane domains, face the cytosolic leaflet of the plasma membrane at the site of bacterial attachment, while the extracellular loop of EspZ is responsible for its strain-specific activity. These results show that EPEC and EHEC acquired a sophisticated mechanism to regulate the effector translocation.
Publication Date: 2-Oct-2012
Date of Acceptance: 4-Sep-2012
URI: http://hdl.handle.net/10044/1/41783
DOI: http://dx.doi.org/10.1128/mBio.00317-12
ISSN: 2161-2129
Publisher: American Society for Microbiology
Journal / Book Title: mBio
Volume: 3
Issue: 5
Copyright Statement: This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Microbiology
MICROBIOLOGY
YERSINIA-PSEUDOTUBERCULOSIS
ENTEROCYTE EFFACEMENT
SUBVERSIVE ELEMENTS
EPITHELIAL-CELLS
GENETIC-LOCUS
EFFECTOR
VIRULENCE
TIR
YOPK
MAP
Bacterial Secretion Systems
Cell Survival
Enterohemorrhagic Escherichia coli
Enteropathogenic Escherichia coli
Epithelial Cells
Escherichia coli Proteins
Gene Expression Regulation, Bacterial
HeLa Cells
Humans
Protein Transport
Virulence Factors
Hela Cells
Epithelial Cells
Humans
Escherichia coli Proteins
Virulence Factors
Cell Survival
Gene Expression Regulation, Bacterial
Protein Transport
Enteropathogenic Escherichia coli
Enterohemorrhagic Escherichia coli
Bacterial Secretion Systems
MAP
0605 Microbiology
Publication Status: Published
Article Number: e00317-12
Appears in Collections:Faculty of Natural Sciences



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