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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adhesins, Bacterial / chemistry
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Adhesins, Bacterial / genetics
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Adhesins, Bacterial / physiology*
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Amino Acid Sequence
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Animals
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Bacterial Adhesion / genetics
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Bacterial Adhesion / physiology*
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Bacterial Outer Membrane Proteins / chemistry
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Bacterial Outer Membrane Proteins / genetics
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Bacterial Outer Membrane Proteins / physiology*
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Caenorhabditis elegans / microbiology
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Escherichia coli / physiology
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Genome, Bacterial
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Gram-Negative Bacteria / genetics
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Gram-Negative Bacteria / pathogenicity*
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Gram-Negative Bacteria / physiology*
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Gram-Negative Bacterial Infections / microbiology
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Gram-Negative Bacterial Infections / physiopathology
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HeLa Cells
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Host-Pathogen Interactions / physiology*
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Humans
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Molecular Sequence Data
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Phylogeny
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Protein Interaction Domains and Motifs
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Sequence Homology, Amino Acid
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Vibrio cholerae / genetics
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Vibrio cholerae / pathogenicity
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Vibrio cholerae / physiology
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Vibrio parahaemolyticus / genetics
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Vibrio parahaemolyticus / pathogenicity
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Vibrio parahaemolyticus / physiology
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Virulence / genetics
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Virulence / physiology
Substances
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Adhesins, Bacterial
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Bacterial Outer Membrane Proteins