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PLoS Negl Trop Dis. 2017 May 22;11(5):e0005586. doi: 10.1371/journal.pntd.0005586. eCollection 2017 May.

Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions.

Author information

1
Molecular Microbiology and Microbial Pathogenesis Program, Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
2
Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddrb), Mohakhali, Dhaka, Bangladesh.
3
Division of Infectious Disease, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
4
Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States of America.
5
Department of Molecular Microbiology, Washington University in Saint Louis, Saint Louis, Missouri, United States of America.
6
Center for Women's Infectious Disease Research (CWIDR), Washington University in Saint Louis, Saint Louis, Missouri, United States of America.
7
Medicine Service, Veterans Affairs Medical Center, Saint Louis, Missouri, United States of America.

Abstract

Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse pathogens.

PMID:
28531220
PMCID:
PMC5456409
DOI:
10.1371/journal.pntd.0005586
[Indexed for MEDLINE]
Free PMC Article

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