title: Outer membrane adhesion factor multivalent adhesion molecule 7 initiates host cell binding during infection by gram-negative pathogens.
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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Krachler
authors.forename: Hyeilin
authors.initials: H
authors.lastname: Ham
authors.forename: Kim
authors.initials: K
authors.lastname: Orth
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000382:microbiology; D004926:Escherichia coli / Q000502:physiology; D016680:Genome, Bacterial; D006090:Gram-Negative Bacteria / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology / Q000503:physiopathology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D054730:Protein Interaction Domains and Motifs; D017386:Sequence Homology, Amino Acid; D014734:Vibrio cholerae / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D014736:Vibrio parahaemolyticus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D014774:Virulence / Q000235:genetics / Q000502:physiology
chemical_list: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins