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

Cepeda-Molero, Massiel, Berger, Cedric N., Walsham, Alistair D. S., Ellis, Samuel J., Wemyss-Holden, Simon, Schüller, Stephanie, Frankel, Gad and Fernández, Luis Ángel (2017) Attaching and effacing (A/E) lesion formation by enteropathogenic E. coli on human intestinal mucosa is dependent on non-LEE effectors. PLoS Pathogens, 13 (10). ISSN 1553-7374

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    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.

    Item Type: Article
    Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
    University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
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    Depositing User: Pure Connector
    Date Deposited: 16 Nov 2017 06:06
    Last Modified: 25 Jul 2018 14:17
    URI: https://ueaeprints.uea.ac.uk/id/eprint/65472
    DOI: 10.1371/journal.ppat.1006706

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