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Attaching and effacing (A/E) lesion formation by enteropathogenic E. coli on human intestinal mucosa is dependent on non-LEE effectors

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Title: Attaching and effacing (A/E) lesion formation by enteropathogenic E. coli on human intestinal mucosa is dependent on non-LEE effectors
Authors: Cepeda-Molero, M
Berger, CN
Walsham, ADS
Ellis, SJ
Wemyss-Holden, S
Schueller, S
Frankel, G
Angel Fernandez, L
Item Type: Journal Article
Abstract: Enteropathogenic E. coli (EPEC) is a human pathogen that causes acute and chronic pediatric diarrhea. The hallmark of EPEC infection is the formation of attaching and effacing (A/E) lesions in the intestinal epithelium. Formation of A/E lesions is mediated by genes located on the pathogenicity island locus of enterocyte effacement (LEE), which encode the adhesin intimin, a type III secretion system (T3SS) and six effectors, including the essential translocated intimin receptor (Tir). Seventeen additional effectors are encoded by genes located outside the LEE, in insertion elements and prophages. Here, using a stepwise approach, we generated an EPEC mutant lacking the entire effector genes (EPEC0) and intermediate mutants. We show that EPEC0 contains a functional T3SS. An EPEC mutant expressing intimin but lacking all the LEE effectors but Tir (EPEC1) was able to trigger robust actin polymerization in HeLa cells and mucin-producing intestinal LS174T cells. However, EPEC1 was unable to form A/E lesions on human intestinal in vitro organ cultures (IVOC). Screening the intermediate mutants for genes involved in A/E lesion formation on IVOC revealed that strains lacking non-LEE effector/s have a marginal ability to form A/E lesions. Furthermore, we found that Efa1/LifA proteins are important for A/E lesion formation efficiency in EPEC strains lacking multiple effectors. Taken together, these results demonstrate the intricate relationships between T3SS effectors and the essential role non-LEE effectors play in A/E lesion formation on mucosal surfaces.
Issue Date: 30-Oct-2017
Date of Acceptance: 20-Oct-2017
URI: http://hdl.handle.net/10044/1/56472
DOI: https://dx.doi.org/10.1371/journal.ppat.1006706
ISSN: 1553-7366
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS Pathogens
Volume: 13
Issue: 10
Copyright Statement: © 2017 Cepeda-Molero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 107057/Z/15/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
ENTEROHEMORRHAGIC ESCHERICHIA-COLI
III SECRETION SYSTEMS
EPITHELIAL-CELLS
IN-VITRO
ENTEROCYTE EFFACEMENT
PATHOGENICITY ISLAND
BACTERIAL EFFECTOR
MAMMALIAN-CELLS
EX-VIVO
TRANSLOCATION
Adhesins, Bacterial
Carrier Proteins
Enterocytes
Escherichia coli
Gene Expression Regulation, Bacterial
Genomic Islands
Humans
Intestinal Mucosa
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: e1006706
Appears in Collections:Faculty of Natural Sciences



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