title: The T3SS effector EspT defines a new category of invasive enteropathogenic E. coli (EPEC) which form intracellular actin pedestals.
abstract: Enteropathogenic Escherichia coli (EPEC) strains are defined as extracellular pathogens which nucleate actin rich pedestal-like membrane extensions on intestinal enterocytes to which they intimately adhere. EPEC infection is mediated by type III secretion system effectors, which modulate host cell signaling. Recently we have shown that the WxxxE effector EspT activates Rac1 and Cdc42 leading to formation of membrane ruffles and lamellipodia. Here we report that EspT-induced membrane ruffles facilitate EPEC invasion into non-phagocytic cells in a process involving Rac1 and Wave2. Internalized EPEC resides within a vacuole and Tir is localized to the vacuolar membrane, resulting in actin polymerization and formation of intracellular pedestals. To the best of our knowledge this is the first time a pathogen has been shown to induce formation of actin comets across a vacuole membrane. Moreover, our data breaks the dogma of EPEC as an extracellular pathogen and defines a new category of invasive EPEC.
authors.affiliation: Centre for Molecular Microbiology and Infection, Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Bulgin
authors.forename: Ana
authors.initials: A
authors.lastname: Arbeloa
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Valerie F
authors.initials: VF
authors.lastname: Crepin
authors.forename: Benoit
authors.initials: B
authors.lastname: Raymond
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000818:Animals; D018938:Caco-2 Cells; D002462:Cell Membrane; D054308:Enteropathogenic Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D014617:Vacuoles / Q000382:microbiology; D014774:Virulence; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D029968:Escherichia coli Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; C543138:espT protein, E coli; D020830:rac1 GTP-Binding Protein