title: The fibronectin-binding protein Fnm contributes to adherence to extracellular matrix components and virulence of Enterococcus faecium.
abstract: The interaction between bacteria and fibronectin is believed to play an important role in the pathogenicity of clinically important Gram-positive cocci. In the present study, we identified a gene encoding a predicted fibronectin-binding protein of Enterococcus faecium (fnm), a homologue of Streptococcus pneumoniae pavA, in the genomes of E. faecium strain TX82 and all other sequenced E. faecium isolates. Full-length recombinant Fnm from strain TX82 bound to immobilized fibronectin in a concentration-dependent manner and also appeared to bind collagen type V and laminin, but not other proteins, such as transferrin, heparin, bovine serum albumin, mucin, or collagen IV. We demonstrated that the N-terminal fragment of Fnm is required for full fibronectin binding, since truncation of this region caused a 2.4-fold decrease (P < 0.05) in the adhesion of E. faecium TX82 to fibronectin. Deletion of fnm resulted in a significant reduction (P < 0.001) in the ability of the mutant, TX6128, to bind fibronectin relative to that of the wild-type strain; in situ reconstitution of fnm in the deletion mutant strain restored adherence. In addition, the Δfnm mutant was highly attenuated relative to TX82 (P ≤ 0.0001) in a mixed-inoculum rat endocarditis model. Taken together, these results demonstrate that Fnm affects the adherence of E. faecium to fibronectin and is important in the pathogenesis of experimental endocarditis.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Sudha R
authors.initials: SR
authors.lastname: Somarajan
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Sabina Leanti
authors.initials: SL
authors.lastname: La Rosa
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center, Houston, Texas, USA Center for the Study of Emerging and Re-emerging Pathogens, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Kavindra V
authors.initials: KV
authors.lastname: Singh
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Jung H
authors.initials: JH
authors.lastname: Roh
authors.affiliation: Center for Infectious and Inflammatory Diseases, Institute for Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, USA.
authors.forename: Magnus
authors.initials: M
authors.lastname: Höök
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Health Science Center, Houston, Texas, USA Center for the Study of Emerging and Re-emerging Pathogens, University of Texas Health Science Center, Houston, Texas, USA Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, Texas, USA bem.asst@uth.tmc.edu.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Murray
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D024062:Collagen Type V / Q000378:metabolism; D004697:Endocarditis, Bacterial / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016984:Enterococcus faecium / Q000235:genetics / Q000472:pathogenicity*; D005353:Fibronectins / Q000378:metabolism; D016680:Genome, Bacterial; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D055767:Immobilized Proteins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D024062:Collagen Type V; D005353:Fibronectins; D055767:Immobilized Proteins; D007797:Laminin; C500900:PavA protein, Streptococcus pneumoniae; D011994:Recombinant Proteins