title: Staphylococcus aureus SigB activity promotes a strong fibronectin-bacterium interaction which may sustain host tissue colonization by small-colony variants isolated from cystic fibrosis patients.
abstract: Genes encoding cell-surface proteins regulated by SigB are stably expressed in Staphylococcus aureus small-colony variants (SCVs) isolated from cystic fibrosis (CF) patients. Our hypothesis is that CF-isolated SCVs are locked into a colonization state by sustaining the expression of adhesins such as fibronectin-binding proteins (FnBPs) throughout growth. Force spectroscopy was used to study the fibronectin-FnBPs interaction among strains varying for their SigB activity. The fibronectin-FnBPs interaction was described by a strength of 1000+/-400 pN (pulling rate of 2 microm s(-1)), an energetic barrier width of 0.6+/-0.1 A and an off-rate below 2 x 10(-4) s(-1). A CF-isolated SCV highly expressed fnbA throughout growth and showed a sustained capacity to bind fibronectin, whereas a prototypic strain showed a reduced frequency of fibronectin-binding during the stationary growth phase when its fnbA gene was down-regulated. Reduced expression of fnbA was observed in sigB mutants, which was associated with an overall decrease adhesion to fibronectin. These results suggest that the fibronectin-FnBPs interaction plays a role in the formation of a mechanically resistant adhesion of S. aureus to host tissues and supports the hypothesis that CF-isolated SCVs are locked into a colonization state as a result of a sustained SigB activity.
authors.affiliation: Centre d'Etude et de Valorisation de la Diversité Microbienne, Département de biologie, Faculté des sciences, Université de Sherbrooke, Sherbrooke, QC, J1K 2R1, Canada.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mitchell
authors.forename: Charles-Antoine
authors.initials: CA
authors.lastname: Lamontagne
authors.forename: Eric
authors.initials: E
authors.lastname: Brouillette
authors.forename: Gilles
authors.initials: G
authors.lastname: Grondin
authors.forename: Brian G
authors.initials: BG
authors.lastname: Talbot
authors.forename: Michel
authors.initials: M
authors.lastname: Grandbois
authors.forename: François
authors.initials: F
authors.lastname: Malouin
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism / Q000382:microbiology*; D005353:Fibronectins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D012808:Sigma Factor / Q000378:metabolism*; D013211:Staphylococcus aureus
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D005353:Fibronectins; C079011:SigB protein, Bacteria; D012808:Sigma Factor; C078635:fibronectin-binding proteins, bacterial