Enterotoxigenic Escherichia coli EtpA mediates adhesion between flagella and host cells

Nature. 2009 Jan 29;457(7229):594-8. doi: 10.1038/nature07568. Epub 2008 Dec 7.

Abstract

Adhesion to epithelial cells and flagella-mediated motility are critical virulence traits for many Gram-negative pathogens, including enterotoxigenic Escherichia coli (ETEC), a major cause of diarrhoea in travellers and children in developing countries. Many flagellated pathogens export putative adhesins belonging to the two-partner secretion (TPS) family. However, the actual function of these adhesins remains largely undefined. Here we demonstrate that EtpA, a TPS exoprotein adhesin of enterotoxigenic E. coli, mimics and interacts with highly conserved regions of flagellin, the major subunit of flagella, and that these interactions are critical for adherence and intestinal colonization. Although conserved regions of flagellin are mostly buried in the flagellar shaft, our results suggest that they are at least transiently exposed at the tips of flagella where they capture EtpA adhesin molecules for presentation to eukaryotic receptors. Similarity of EtpA to molecules encoded by other motile pathogens suggests a potential common pattern for bacterial adhesion, whereas participation of conserved regions of flagellin in adherence has implications for development of vaccines for Gram-negative pathogens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacterial Adhesion*
  • Bacterial Vaccines / immunology
  • Cell Line
  • Conserved Sequence
  • Enterotoxigenic Escherichia coli / cytology*
  • Enterotoxigenic Escherichia coli / metabolism*
  • Enterotoxigenic Escherichia coli / pathogenicity
  • Epithelial Cells / microbiology*
  • Escherichia coli Infections / immunology
  • Escherichia coli Infections / prevention & control
  • Escherichia coli Proteins / metabolism*
  • Flagella / chemistry
  • Flagella / metabolism*
  • Flagellin / chemistry
  • Flagellin / immunology
  • Flagellin / metabolism
  • Host-Pathogen Interactions*
  • Intestine, Small / cytology
  • Intestine, Small / microbiology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Protein Binding

Substances

  • Bacterial Vaccines
  • Escherichia coli Proteins
  • EtpA protein, E coli
  • Membrane Glycoproteins
  • Flagellin