title: A role for sigma factor B in the emergence of Staphylococcus aureus small-colony variants and elevated biofilm production resulting from an exposure to aminoglycosides.
abstract: Staphylococcus aureus small-colony variants (SCVs) and biofilms are linked to chronic infections. It is known that the presence of aminoglycoside antibiotics may contribute to the emergence of SCVs and it is thought that molecular mechanisms are involved in the ability of S. aureus to adopt this phenotype. No study has addressed the possible role of the stress- and colonization-related alternative sigma factor B (SigB) in the emergence of SCVs, although a sustained SigB activity was reported in these variants. Here, we demonstrate that SigB is involved in the emergence of SCVs resulting from an exposure to a sub-inhibitory concentration of aminoglycosides. Monitoring of gene expression in an aminoglycoside-treated prototypical strain or in clinical SCVs showed the activation of SigB, whereas the accessory gene regulator (agr) system was not. Furthermore, gentamicin-treated prototypical bacteria and SCVs had an increased ability to form biofilm only in a SigB functional background. The administration of a sub-inhibitory concentration of gentamicin significantly increased the formation of SCVs for a prototypical strain but not for the sigB mutant in a mouse model of S. aureus-induced mastitis. Collectively, our results show that SigB may positively influence the appearance of S. aureus SCVs and the production of biofilm upon aminoglycoside exposure.
authors.affiliation: Centre d'Etude et de Valorisation de la Diversité Microbienne (CEVDM), Département de biologie, Faculté des sciences, Boul. Université, Université de Sherbrooke, Sherbrooke, Canada. Gabriel.Mitchell@USherbrooke.ca
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mitchell
authors.forename: Eric
authors.initials: E
authors.lastname: Brouillette
authors.forename: David Lalonde
authors.initials: DL
authors.lastname: Séguin
authors.forename: Ann-Elise
authors.initials: AE
authors.lastname: Asselin
authors.forename: Christian Lebeau
authors.initials: CL
authors.lastname: Jacob
authors.forename: François
authors.initials: F
authors.lastname: Malouin
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000502:physiology*; D018441:Biofilms / Q000254:growth & development*; D015169:Colony Count, Microbial; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D008413:Mastitis / Q000382:microbiology; D051379:Mice; D012808:Sigma Factor / Q000502:physiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D013312:Stress, Physiological
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C079011:SigB protein, Bacteria; D012808:Sigma Factor