title: Meningococcal surface fibril (Msf) binds to activated vitronectin and inhibits the terminal complement pathway to increase serum resistance.
abstract: Complement evasion is an important survival strategy of Neisseria meningitidis (Nm) during colonization and infection. Previously, we have shown that Nm Opc binds to serum vitronectin to inhibit complement-mediated killing. In this study, we demonstrate meningococcal interactions with vitronectin via a novel adhesin, Msf (meningococcal surface fibril, previously NhhA or Hsf). As with Opc, Msf binds preferentially to activated vitronectin (aVn), engaging at its N-terminal region but the C-terminal heparin binding domain may also participate. However, unlike Opc, the latter binding is not heparin-mediated. By binding to aVn, Msf or Opc can impart serum resistance, which is further increased in coexpressers, a phenomenon dependent on serum aVn concentrations. The survival fitness of aVn-binding derivatives was evident from mixed population studies, in which msf/opc mutants were preferentially depleted. In addition, using vitronectin peptides to block Msf-aVn interactions, aVn-induced inhibition of lytic C5b-9 formation and of serum killing could be reversed. As Msf-encoding gene is ubiquitous in the meningococcal strains examined and is expressed in vivo, serum resistance via Msf may be of significance to meningococcal pathogenesis. The data imply that vitronectin binding may be an important strategy for the in vivo survival of Nm for which the bacterium has evolved redundant mechanisms.
authors: Schools of Cellular & Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors: Natalie J
authors: NJ
authors: Griffiths
authors: Darryl J
authors: DJ
authors: Hill
authors: Elena
authors: E
authors: Borodina
authors: Richard B
authors: RB
authors: Sessions
authors: Nathalie I
authors: NI
authors: Devos
authors: Christiane M
authors: CM
authors: Feron
authors: Jan T
authors: JT
authors: Poolman
authors: Mumtaz
authors: M
authors: Virji
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D001770:Blood Bactericidal Activity; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors*; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D008565:Membrane Proteins / Q000378:metabolism; D008958:Models, Molecular; D009345:Neisseria meningitidis / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D019096:Vitronectin / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D015938:Complement Membrane Attack Complex; C102673:Hsf protein, bacteria; D008565:Membrane Proteins; D019096:Vitronectin