The discrepancy may suggest that the regulatory activity of AirR is strain specific. Why AirSR acts differently
in different strains is still not clear. Our speculation is that inactivation of sigma B in NCTC8325 may contribute to the different activity of AirSR in NCTC8325 and Newman. But this speculation needs further study. WalKR is an important TCS that positively controls cell wall biosynthesis and turnover, Tanespimycin including directly controlling lytM [12]. Alterations in the expression of WalKR as well as WalKR mutations at amino acid sequence can lead to a change in susceptibility to vancomycin [19, 30]. AirSR and WalKR exhibit similar functions. Our microarray data indicate that the WalKR expression level is unchanged in the airSR mutant, and there is no report so far that WalKR regulates AirSR, suggesting that the two TCSs
may regulate cell wall biosynthesis independently. see more Conclusions The airSR mutant exhibited reduced autolysis and down-regulation in many cell wall metabolism-related genes in S. aureus NCTC8325. And AirR can directly bind to the promoter region of some of these cell wall metabolism genes. These findings demonstrate that AirSR is a positive regulator in cell wall biosynthesis and turnover in S. aureus NCTC8325. The airSR mutant exhibited reduced viability in the presence of vancomycin, suggesting that AirSR could be a new target for controlling S. aureus infection. Acknowledgments The authors thank the Network on Antimicrobial TPX-0005 Resistance in Staphylococcus aureus (NARSA) for providing the bacterial strains. This study was supported
by the National Natural Science Foundation of China (grants 31070116 and 81371850). Electronic supplementary material Additional file 1: Correlationship between microarray data and the real-time RT PCR result. The transcriptional level of 11 genes from both microarray and real-time RT PCR were log2 transformed and plotted against each other. A linear fit analysis 2-hydroxyphytanoyl-CoA lyase was performed to check the correlation between the two methods. R2 = 0.9678. (TIFF 124 KB) Additional file 2: EMSA of cap promoter with unphosphorylated and phosphorylated AirR. The first lane was the free DNA probe (2 nM); the second to fourth lanes were the DNA probe with increasing amounts of unphosphorylated AirR (0.25, 0.5, and 1 μM); the fifth to seventh lanes were the DNA probe with increasing amounts of lithium potassium acetyl phosphate phosphorylated AirR (0.25, 0.5, and 1 μM); the eighth to tenth lanes were the DNA probe with increasing amounts of AirS phosphorylated AirR (0.25, 0.5, and 1 μM). (TIFF 145 KB) Additional file 3: Phylogenetic footprinting of AirR binding sequences.