title: Two-component system RgfA/C activates the fbsB gene encoding major fibrinogen-binding protein in highly virulent CC17 clone group B Streptococcus.
abstract: Group B streptococcus (GBS) strains with the highest ability to bind to human fibrinogen belong to the highly invasive clonal complex (CC) 17. To investigate the fibrinogen-binding mechanisms of CC17 strains, we determined the prevalence of fibrinogen-binding genes (fbsA and fbsB), and fbs regulator genes (rogB encoding an fbsA activator, rovS encoding an fbsA repressor and rgf encoding a two-component system [TCS] whose role on fbs genes was not determined yet) in a collection of 134 strains representing the major CCs of the species. We showed that specific gene combinations were related to particular CCs; only CC17 strains contained the fbsA, fbsB, and rgf genes combination. Non polar rgfAC deletion mutants of three CC17 serotype III strains were constructed. They showed a 3.2- to 5.1-fold increase of fbsA transcripts, a 4.8- to 6.7-fold decrease of fbsB transcripts, and a 52% to 68% decreased fibrinogen-binding ability, demonstrating that the RgfA/RgfC TCS inhibits the fbsA gene and activates the fbsB gene. The relative contribution of the two fbs genes in fibrinogen-binding ability was determined by constructing isogenic fbsA, fbsB, deletion mutants of the three CC17 strains. The ability to bind to fibrinogen was reduced by 49% to 57% in ΔfbsA mutants, and by 78% to 80% in ΔfbsB mutants, suggesting that FbsB protein plays a greater role in the fibrinogen-binding ability of CC17 strains. Moreover, the relative transcription level of fbsB gene was 9.2- to 12.7-fold higher than that of fbsA gene for the three wild type strains. Fibrinogen-binding ability could be restored by plasmid-mediated expression of rgfAC, fbsA, and fbsB genes in the corresponding deletion mutants. Thus, our results demonstrate that a specific combination of fbs genes and fbs regulator genes account for the high fibrinogen-binding ability of CC17 strains that may participate to their enhanced invasiveness for neonates as compared to strains of other CCs.
authors.affiliation: Equipe d'Accueil 3854 Bactéries et risque materno-fœtal, Institut Fédératif de Recherche 136 Agents Transmissibles et Infectiologie, UFR Médecine, Université François Rabelais de Tours, Tours, France.
authors.forename: Rim
authors.initials: R
authors.lastname: Al Safadi
authors.forename: Laurent
authors.initials: L
authors.lastname: Mereghetti
authors.forename: Mazen
authors.initials: M
authors.lastname: Salloum
authors.forename: Marie-Frédérique
authors.initials: MF
authors.lastname: Lartigue
authors.forename: Isabelle
authors.initials: I
authors.lastname: Virlogeux-Payant
authors.forename: Roland
authors.initials: R
authors.lastname: Quentin
authors.forename: Agnès
authors.initials: A
authors.lastname: Rosenau
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002999:Clone Cells; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D030781:Organisms, Genetically Modified; D011485:Protein Binding; D013292:Streptococcus agalactiae / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C487204:FbsB protein, Streptococcus agalactiae; D055767:Immobilized Proteins; D050505:Mutant Proteins; D005340:Fibrinogen