Journal Article

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

Krachler, Anne Marie, Orth, Kim, Ham, Hyeilin

2011

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: 3T3 cells / Adhesins, Bacterial - chemistry / Adhesins, Bacterial - genetics / Adhesins, Bacterial - physiology / Adhesion / Amino Acid Sequence / Animals / avirulent strains / Bacteria / Bacterial adhesion / Bacterial Adhesion - genetics / Bacterial Adhesion - physiology / Bacterial diseases / bacterial infections / Bacterial Outer Membrane Proteins - chemistry / Bacterial Outer Membrane Proteins - genetics / Bacterial Outer Membrane Proteins - physiology / Biological Sciences / Caenorhabditis elegans - microbiology / Cell adhesion & migration / Cell adhesion molecules / Cell membranes / Cytotoxicity / Escherichia coli - physiology / Fibronectin / fibronectins / Genome, Bacterial / Gram-negative bacteria / 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 relationships / Host-Pathogen Interactions - physiology / Humans / Infection / Infections / Lipids / mammals / Membranes / Molecular Sequence Data / Molecules / Nematoda / nematode infections / Outer membranes / Pathogens / phosphatidic acid / Phylogeny / Protein Interaction Domains and Motifs / Proteins / Sequence Homology, Amino Acid / Vibrio cholerae - genetics / Vibrio cholerae - pathogenicity / Vibrio cholerae - physiology / Vibrio parahaemolyticus - genetics / Vibrio parahaemolyticus - pathogenicity / Vibrio parahaemolyticus - physiology / virulence / Virulence - genetics / Virulence - physiology / virulence factors