sarU , a sarA Homolog, Is Repressed by SarT and Regulates Virulence Genes in Staphylococcus aureus

Abstract

ABSTRACT In searching the Staphylococcus aureus genome, we previously identified sarT , a homolog of sarA, which encodes a repressor for α-hemolysin synthesis. Adjacent but transcribed divergently to sarT is sarU, which encodes a 247-residue polypeptide, almost twice the length of SarA. Sequence alignment disclosed that SarU, like SarS, which is another SarA homolog, could be envisioned as a molecule with two halves, with each half being homologous to SarA. SarU, as a member of the SarA family proteins, disclosed conservation of basic residues within the helix-turn-helix motif and within the beta hairpin loop, two putative DNA binding domains within this protein family. The transcription of sarU is increased in a sarT mutant. Gel shift and transcriptional fusion studies revealed that SarT can bind to the sarU promoter region, probably acting as a repressor for sarU transcription. The expression of RNAII and RNAIII of agr is decreased in a sarU mutant. As RNAIII expression is up-regulated in a sarT mutant, we hypothesize that sarT may down regulate agr RNAIII expression by repressing sarU , a positive activator of agr expression. We propose that, in addition to the quorum sensing effect of the autoinducing peptide of agr , the sarT - sarU pathway may represent a secondary amplification loop whereby the expression of agr (e.g., those found in vivo) might repress sarT , leading to increased expression of sarU . Elevated sarU expression would result in additional amplification of the original agr signal.