GSE114706
Changes in the transcriptome of S. aureus SH1000 containing a nisin resistance mutation in nsaS
We have demonstrated previously that high-level resistance to nisin can occur in Staphylococcus aureus as a consequence of a single non-synonymous mutation in nsaS, which encodes a putative sensor kinase. To explore the mechanism by which this mutation confers high-level resistance we compared global transcriptomes of SH1000 and SH1000 (NsaS A208E) using RNAseq. This process identified several genes to be upregulated in SH1000 (NsaS A208E), including members of the NsaRS regulon which encode VraDE and BraDE, two putative ABC-transporters and are known to provide intrinsic nisin resistance. Gene deletion and complementation experiments revealed that both BraDE and VraDE are essential to high-level nisin resistance, with BraDE required for signal transduction through NsaRS, and VraDE directly responsible for nisin detoxification. Overall design: Total RNA was extracted from explonentially-growing cultures of SH1000 (x2 replicates) and SH1000 (NsaS A208E) (x3 replicates) and was subjected to sequencing using an Illumina NextSeq 500