title: sarU, a sarA homolog, is repressed by SarT and regulates virulence genes in Staphylococcus aureus.
abstract: In searching the Staphylococcus aureus genome, we previously identified sarT, a homolog of sarA, which encodes a repressor for alpha-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.
authors.affiliation: Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA. Adhar.C.Manna@Dartmouth.EDU
authors.forename: Adhar C
authors.initials: AC
authors.lastname: Manna
authors.forename: Ambrose L
authors.initials: AL
authors.lastname: Cheung
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000378:metabolism; D012329:RNA, Bacterial / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D016372:RNA, Antisense; D012329:RNA, Bacterial; C096035:RNAIII, Staphylococcus aureus; D012097:Repressor Proteins; C088021:SarA protein, bacterial; C433204:SarH3 protein, Staphylococcus aureus; C470922:SarU protein, Staphylococcus aureus; D015534:Trans-Activators