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Journal of Bacteriology, January 2006, p. 64-76, Vol. 188, No. 1
0021-9193/06/$08.00+0     doi:10.1128/JB.188.1.64-76.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transcription of Virulence Factors in Staphylococcus aureus Small-Colony Variants Isolated from Cystic Fibrosis Patients Is Influenced by SigB

Hélène Moisan,1 Eric Brouillette,1 Christian Lebeau Jacob,1 Philippe Langlois-Bégin,1 Sophie Michaud,2 and François Malouin1*

Centre d'Étude et de Valorisation de la Diversité Microbienne, Département de Biologie, Faculté des Sciences,1 Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke J1K 2R1, QC, Canada2

Received 12 August 2005/ Accepted 7 October 2005

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.

* Corresponding author. Mailing address: Département de Biologie, Faculté des Sciences, Université de Sherbrooke, 2500 Boul. Université, Sherbrooke J1K 2R1, QC, Canada. Phone: (819) 821-8000, ext. 1202. Fax: (819) 821-8049. E-mail: francois.malouin{at}usherbrooke.ca.

Journal of Bacteriology, January 2006, p. 64-76, Vol. 188, No. 1
0021-9193/06/$08.00+0     doi:10.1128/JB.188.1.64-76.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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