Moreover, in our experiment, the transcriptional response of these genes is seen to be time and concentration dependent (Table 2). Their expression is controlled mainly by the vraSR two component system and it has been shown that the VraSR regulon is induced specifically only by cell-wall-active antibiotics [10]. Fosfomycin strongly induced the vraS (Table 2) and vraR

(Additional file 1) genes and many of the genes they regulate – not only cell wall synthesis genes but also those for chaperones, heat shock proteins and osmoprotectant transporters. The rib and ure operons, involved in cofactor biosynthesis and PX-478 concentration urea degradation and, which were induced by some cell-wall-active antibiotics, were also induced at the latest time point in our experiment. Table 2 Expression of “”cell wall stress stimulon”" genes: comparison of current study with published results in the Captisol mouse SAMMD. N315 LOCUS a Gene Name b Expression fold change c Gene Product Description e TIGR Functional Group     t10c1 t20c1 t40c1 t10c4 t20c4 t40c4 Cell wall active antibiotics d     SA0909 fmt     2.65   1.83 3.23 + Fmt, autolysis and methicillin resistant-related H 89 in vitro protein Cell envelope SA1549       1.38   0.63 1.87 + hypothetical protein, similar to serine proteinase Protein fate SA1659 prsA     1.57   0.94 1.89 + peptidyl-prolyl

cis/trans isomerase homolog Protein fate SA1691 sgtB   0.37 2.37   1.31 3.14 + hypothetical protein, similar to penicillin-binding protein 1A/1B Cell envelope SA1701 vraS   0.28 2.05   1.21 2.93 + two-component sensor histidine kinase Cellular processes SA1702       2.25   1.29 3.34 + conserved hypothetical protein Unclassified SA1703       2.63   1.47 3.54 + hypothetical protein Unclassified SA1712       0.69   0.41 1.60 + conserved hypothetical protein Unclassified SA1926 murZ     0.94   0.51 1.45 + UDP-N-acetylglucosamine 1-carboxylvinyl transferase 2 Cell

envelope SA2103       1.58   0.87 2.11 + hypothetical protein, similar to lyt divergon expression Regulatory functions SA2146 tcaA   0.27 2.07   1.27 2.69 + TcaA protein Energy metabolism SA2220       0.95   0.47 1.48 + hypothetical protein Energy metabolism SA2221       1.92   0.96 2.59 + hypothetical protein Unclassified Rebamipide SA2297             0.37 + hypothetical protein, similar to GTP-pyrophosphokinase Unclassified SA2343   -0.73 2.11 7.08   5.50 7.62 + hypothetical protein Unclassified SA0423       -0.47     -1.34 – hypothetical protein, similar to autolysin (N-acetylmuramoyl-L-alanine amidase) Unclassified SA0905 atl     -0.54     -1.24 – autolysin Cell envelope         -0.51     -1.19       a S. aureus N315 genome ORF locus. b Previously described gene name. c Gene expression log2 fold change of treated vs. non-treated bacteria. Abbreviations correspond to experimental design points. d Previously reported expression increase (+) or decrease (-) of cell-wall-antibiotic treated vs. non-treated bacteria. e Gene product functional annotation.