, 2007; Belcheva & Golemi-Kotra, 2008; Eldholm et al., 2010; Belcheva et al., 2012). There is a wide variation in the fold-induction levels of different CWSS selleck chemicals llc genes, which is probably linked to the specificity of VraR-binding, although the exact VraR-binding consensus and the influence of specific nucleotide differences on expression and induction of different CWSS genes has not been thoroughly analysed (Martinez

et al., 2007; Belcheva & Golemi-Kotra, 2008; Belcheva et al., 2012). The magnitude of CWSS induction strongly depends on the class and concentration of cell wall antibiotics (Dengler et al., 2011). Disruption of wall teichoic acid (WTA) synthesis by targocil, which inhibits the WTA transporter TarG (TagG), was also shown to activate the CWSS (Campbell et al., 2012). WTA are anionic glycopolymers that are attached to the peptidoglycan www.selleckchem.com/products/PD-0325901.html of Gram-positive bacteria via a phosphodiester linkage, and they can constitute up to 60%

of the total cell wall biomass. WTA of B. subtilis are composed of poly(glycerol phosphate) and poly(ribitol phosphate), whereas S. aureus contains mainly poly(ribitol phosphate) WTA. The biosynthesis of WTA is catalysed by tag (teichoic acid glycerol) or tar (teichoic acid ribitol) genes in B. subtilis and S. aureus, respectively (reviewed in Swoboda et al., 2010). Besides the induction by cell wall active antibiotics, VraSR signal transduction is also triggered by internal disruption of cell wall synthesis caused by the depletion of essential Acyl CoA dehydrogenase cell wall biosynthesis enzymes such as MurA, MurZ, MurB (Blake et al., 2009), MurF (Sobral et al., 2007), PBP2 (Gardete et al., 2006) or depletion of enzymes involved in mevalonate biosynthesis, the direct precursor for undecaprenyl phosphate lipid carrier synthesis (Balibar et al., 2009). Induction of the CWSS enhances intrinsic resistance/tolerance to almost all cell wall damaging agents, regardless of their target or mode of action (Dengler et al., 2011; McCallum et al., 2011). Members of the CWSS directly linked to peptidoglycan

synthesis, such as PBP2, FmtA, MurZ and SgtB, are thought to contribute to the stress response by stimulating cell wall synthesis (Cui et al., 2009; Kato et al., 2010; Mehta et al., 2012). It is predicted that CWSS genes with unknown or poorly characterized functions are also likely to contribute to the stress response by directly or indirectly influencing cell wall synthesis. All three S. aureus LytR-CpsA-Psr (LCP) genes, msrR, sa0908 and sa2103, belong to the CWSS (Utaida et al., 2003; McAleese et al., 2006; Over et al., 2011). LCP proteins are unique to bacteria with Gram-positive cell walls (Hübscher et al., 2008; Kawai et al., 2011) and typically contain a short intracellular N-terminal region, a transmembrane domain and a large extracelluar region containing the LCP domain (Hübscher et al., 2008; Kawai et al., 2011). Deletion of LCP proteins in S. aureus alters cell surface properties and decreases virulence.