The impact of
glycopeptide resistance on the molecular regulation of Staphylococcus aureus virulence and attachment to host tissues is poorly documented. We compared stable
teicoplanin-resistant methicillin-resistant S. aureus (MRSA) strain 14-4 with its
teicoplanin-susceptible MRSA parent, strain MRGR3, which exhibits a high degree of virulence in a rat model of chronic
foreign body MRSA
infection. The levels of
fibronectin-mediated adhesion and surface display of
fibronectin-
binding proteins were higher in
teicoplanin-resistant strain 14-4 than in its
teicoplanin-susceptible parent or a
teicoplanin-susceptible revertant (strain 14-4rev) that spontaneously emerged during
tissue cage infection. Quantitative reverse transcription-PCR (qRT-PCR) showed four- and twofold higher steady-state levels of fnbA and fnbB transcripts, respectively, in strain 14-4 than in its
teicoplanin-susceptible counterparts. Analysis of global regulatory activities by qRT-PCR revealed a strong reduction in the steady-state levels of
RNAIII and RNAII in the
teicoplanin-resistant strain compared to in its
teicoplanin-susceptible counterparts. In contrast, sarA
mRNA levels were more than fivefold higher in strain 14-4 than in MRGR3 and 14-4rev. Furthermore, the alternative
transcription factor sigma B had a higher level of functional activity in the
teicoplanin-resistant strain than in its
teicoplanin-susceptible counterparts, as evidenced by significant increases in both the sigma B-dependent asp23
mRNA levels and the sarA P3 promoter-derived transcript levels, as assayed by qRT-PCR and Northern blotting, respectively. These data provide further evidence that the emergence of
glycopeptide resistance is linked by still poorly understood molecular pathways with significant pleiotropic changes in the expression and regulation of some major virulence genes. These molecular and phenotypic changes may have a profound impact on the bacterial adhesion and colonization properties of such multiresistant organisms.