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

Anne Marie Krachler, Hyeilin Ham, Kim Orth

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)11614-11619
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number28
DOIs
StatePublished - Jul 12 2011

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Gram-Negative Bacterial Infections
Membranes
Infection
Nematode Infections
Phosphatidic Acids
Proteins
Virulence Factors
Fibronectins
Virulence
Cell Membrane
Bacteria
Lipids

Keywords

  • Adhesin
  • Bacterial attachment
  • Microbiology

ASJC Scopus subject areas

  • General

Cite this

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AU - Orth, Kim

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AB - 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.

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