Exposure of vancomycin-sensitive Staphylococcus aureus to subinhibitory levels of vancomycin leads to upregulated capsular gene expression

Abstract

Reduced vancomycin susceptibility in Staphylococcus aureus continues to trouble clinical microbiologists and infectious disease specialists. In this study, a vancomycin-susceptible S. aureus (VSSA) strain, which was methicillin-resistant (MRSA), was grown with and without subinhibitory levels of vancomycin, and the transcriptional profiles were determined by microarray analysis. Thirty-six genes were upregulated and 42 genes were down-regulated by more than two-fold (P<0.05) in the presence of vancomycin. Many of these genes are involved in cell-wall biosynthesis and regulation, but of particular interest was the upregulation of genes in the locus responsible for capsule synthesis. Increased capsule production following exposure of MRSA to low levels of vancomycin could explain treatment failure. This suggests that selected genes of the capsule locus could be used as diagnostic targets for monitoring patients undergoing treatment with vancomycin therapy, as an increase in their expression may indicate progressive development of low-level resistance.