title: Role of the serine-rich surface glycoprotein Srr1 of Streptococcus agalactiae in the pathogenesis of infective endocarditis.
abstract: The binding of bacteria to fibrinogen and platelets are important events in the pathogenesis of infective endocarditis. Srr1 is a serine-rich repeat glycoprotein of Streptococcus agalactiae that binds directly to the Aα chain of human fibrinogen. To assess the impact of Srr1 on the pathogenesis of endocarditis due to S. agalactiae, we first examined the binding of this organism to immobilized human platelets. Strains expressing Srr1 had significantly higher levels of binding to human platelets in vitro, as compared with isogenic Δsrr1 mutants. In addition, platelet binding was inhibited by pretreatment with anti-fibrinogen IgG or purified Srr1 binding region. To assess the contribution of Srr1 to pathogenicity, we compared the relative virulence of S. agalactiae NCTC 10/84 strain and its Δsrr1 mutant in a rat model of endocarditis, where animals were co-infected with the WT and the mutant strains at a 1:1 ratio. At 72 h post-infection, bacterial densities (CFU/g) of the WT strain within vegetations, kidneys, and spleens were significantly higher, as compared with the Δsrr1 mutant. These results indicate that Srr1 contributes to the pathogenesis of endocarditis due to S. agalactiae, at least in part through its role in fibrinogen-mediated platelet binding.
authors.affiliation: Division of Infectious Diseases, Veterans Affairs Medical Center and the University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Ho Seong
authors.initials: HS
authors.lastname: Seo
authors.forename: Yan Q
authors.initials: YQ
authors.lastname: Xiong
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sullam
mesh_terms: D018829:Adhesins, Bacterial / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion; D001792:Blood Platelets / Q000382:microbiology; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D005260:Female; D005340:Fibrinogen / Q000737:chemistry / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013290:Streptococcal Infections / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; C524542:Srr-1 protein, Streptococcus agalactiae; D005340:Fibrinogen