title: SarT influences sarS expression in Staphylococcus aureus.
abstract: Staphylococcus aureus is a gram-positive pathogen that is capable of expressing a variety of virulence proteins in response to environmental signals. Virulence protein expression in S. aureus is controlled by a network of regulatory loci including sarA and agr. The sarA/agr network is associated with the expression of cell wall-associated adhesins during exponential growth and the expression of secreted enzymes and toxins in the transition to post-exponential growth. A number of sarA homologs, including sarT and sarS, have been identified in the S. aureus genome. Previous studies have shown that sarA influences expression of both sarT and sarS in the global regulatory network. SarS has been shown to bind to the spa promoter to induce expression of protein A. SarT, one of the SarA homologs that represses hla expression and is repressible by SarA and agr, was found to induce sarS expression in this report. Northern blot analysis of sarS and spa expression in S. aureus RN6390, and the isogenic sarT, sarT sarA, and sarT agr mutants showed that while sarA regulated spa expression directly, the agr locus used sarT as an intermediary to regulate sarS, thus leading to spa repression in agr-activated cells. Gel shift and footprinting analysis showed that SarT binds to the sarS promoter, indicating that the interaction of the sarT gene product with the upstream region of sarS is likely direct. Induction of sarS and spa by SarT in agr(+) strains was confirmed by a tetracycline-inducible system to titrate sarT expression.
authors.affiliation: Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA. Katherine.A.Schmidt@Dartmouth.edu
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Schmidt
authors.forename: Adhar C
authors.initials: AC
authors.lastname: Manna
authors.forename: Ambrose L
authors.initials: AL
authors.lastname: Cheung
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004318:Doxycycline / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013205:Staphylococcal Protein A / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics
chemical_list: C095698:Agr protein, Staphylococcus aureus; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C088021:SarA protein, bacterial; C433204:SarH3 protein, Staphylococcus aureus; C476149:SarS protein, Staphylococcus aureus; D013205:Staphylococcal Protein A; D015534:Trans-Activators; C119204:streptococcal protective antigen; D004318:Doxycycline