当前位置： SCI文献检索 > PLoS Neglected Tropical Diseases期刊下所有文献 > Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions.

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

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.

journal_name

PLoS Negl Trop Dis

journal_title

PLoS neglected tropical diseases

authors

Sheikh A,Rashu R,Begum YA,Kuhlman FM,Ciorba MA,Hultgren SJ,Qadri F,Fleckenstein JM

doi

10.1371/journal.pntd.0005586

subject

Has Abstract

pub_date

2017-05-22 00:00:00

pages

e0005586

issue

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-17-00340

journal_volume

pub_type

杂志文章

在线工具

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