Outer membrane adhesion factor multivalent adhesion molecule 7 initiates host cell binding during infection by gram-negative pathogens

Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11614-9. doi: 10.1073/pnas.1102360108. Epub 2011 Jun 27.

Abstract

The initial binding of bacteria to host cells is crucial to the delivery of virulence factors and thus is a key determinant of the pathogen's success. We report a multivalent adhesion molecule (MAM) that enables a wide range of gram-negative pathogens to establish high-affinity binding to host cells during the early stages of infection. MAM7 binds to the host by engaging in both protein-protein (with fibronectin) and protein-lipid (with phosphatidic acid) interactions with the host cell membrane. We find that MAM7 expression on the outer membrane of a gram-negative pathogen is necessary for virulence in a nematode infection model and for efficient killing of cultured mammalian host cells. Expression of MAM7 on nonpathogenic strains produced a tool that can be used to impede infection by gram-negative bacterial pathogens. Targeting or exploiting MAM7 might prove to be important in combating gram-negative bacterial infections.

Publication types

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

MeSH terms

  • Adhesins, Bacterial / chemistry
  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / physiology*
  • Amino Acid Sequence
  • Animals
  • Bacterial Adhesion / genetics
  • Bacterial Adhesion / physiology*
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / physiology*
  • Caenorhabditis elegans / microbiology
  • Escherichia coli / physiology
  • Genome, Bacterial
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacteria / pathogenicity*
  • Gram-Negative Bacteria / physiology*
  • Gram-Negative Bacterial Infections / microbiology
  • Gram-Negative Bacterial Infections / physiopathology
  • HeLa Cells
  • Host-Pathogen Interactions / physiology*
  • Humans
  • Molecular Sequence Data
  • Phylogeny
  • Protein Interaction Domains and Motifs
  • Sequence Homology, Amino Acid
  • Vibrio cholerae / genetics
  • Vibrio cholerae / pathogenicity
  • Vibrio cholerae / physiology
  • Vibrio parahaemolyticus / genetics
  • Vibrio parahaemolyticus / pathogenicity
  • Vibrio parahaemolyticus / physiology
  • Virulence / genetics
  • Virulence / physiology

Substances

  • Adhesins, Bacterial
  • Bacterial Outer Membrane Proteins