title: Transcription of virulence factors in Staphylococcus aureus small-colony variants isolated from cystic fibrosis patients is influenced by SigB.
abstract: Staphylococcus aureus small-colony variants (SCVs) are believed to account in part for the persistence of S. aureus during chronic infections. Little is understood about the gene expression profile that may explain the phenotype and distinguish SCVs from prototype S. aureus strains. In this study, DNA array transcriptional profiles of clinical SCVs isolated from the airways of cystic fibrosis patients were obtained and compared to those obtained from a laboratory-derived SCV strain (i.e., a respiratory-deficient hemB mutant) and prototype S. aureus strains. The genes commonly up-regulated in both hemB and clinical SCVs were found to be implicated in fermentation and glycolysis pathways. The well-known virulence regulator agr was not activated in SCVs, and such strains had low levels of alpha-toxin (hla) gene expression. Clinical SCVs also had a transcriptional signature of their own. Of striking interest is that many genes, most of them under the positive control of the alternate sigma factor SigB, were specifically up-regulated and differed in that way from that seen in prototype S. aureus and the hemB mutant. Since SigB influences up-regulation of adhesin type genes while indirectly down-regulating exoproteins and toxins, we evaluated the internalization and persistence of SCVs in mammalian cells. Results showed that clinical SCVs persisted much more efficiently in cells than the hemB and prototype strains and that a sigB mutant was a poor persister. Thus, it appears that the agr locus plays a minor role in the regulation of the virulon of SCVs, unlike SigB, which may have a key role in intracellular persistence.
authors.affiliation: Département de Biologie, Faculté des Sciences, Université de Sherbrooke, 2500 Boulevard Université, Sherbrooke J1K 2R1, QC, Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Moisan
authors.forename: Eric
authors.initials: E
authors.lastname: Brouillette
authors.forename: Christian Lebeau
authors.initials: CL
authors.lastname: Jacob
authors.forename: Philippe
authors.initials: P
authors.lastname: Langlois-Bégin
authors.forename: Sophie
authors.initials: S
authors.lastname: Michaud
authors.forename: François
authors.initials: F
authors.lastname: Malouin
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D003550:Cystic Fibrosis / Q000382:microbiology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012808:Sigma Factor / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000145:classification / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; C079011:SigB protein, Bacteria; D012808:Sigma Factor; D015534:Trans-Activators; D037521:Virulence Factors