Manna Adhar C, Cheung Ambrose L
Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, 414 E. Clark Street, Vermillion, SD 57069, USA.
J Bacteriol. 2006 Jun;188(12):4288-99. doi: 10.1128/JB.00297-06.
The expression of genes involved in the pathogenesis of Staphylococcus aureus is known to be controlled by global regulatory loci, including agr, sarA, saeRS, arlRS, and sarA-like genes. As part of our continuing efforts to understand the regulatory mechanisms that involve sarA-like genes, we describe here the characterization of a novel transcriptional regulator called SarX, a member of the SarA protein family. The transcription of sarX was growth phase dependent and was expressed maximally during the stationary phase of growth, which was significantly decreased in the mgrA mutant. MgrA acted as an activator of sarX expression as confirmed by transcriptional fusion and Northern blot analyses. Purified MgrA protein bound to the upstream region of the sarX promoter as demonstrated by gel shift assay. The expression levels of various potential target genes involved in virulence and regulation, specifically those affected by sarA and mgrA, were analyzed with isogenic sarX mutant strains. Our data indicated that SarX acted as a repressor of the agr locus and consequently target genes regulated by the agr system. We propose that SarX is an important regulator in the SarA protein family and may be part of the common pathway by which agr and members of the sarA gene family control virulence in S. aureus.
已知参与金黄色葡萄球菌致病机制的基因表达受全局调控位点控制，包括agr、sarA、saeRS、arlRS和sarA样基因。作为我们持续努力理解涉及sarA样基因的调控机制的一部分，我们在此描述一种名为SarX的新型转录调节因子的特性，它是SarA蛋白家族的成员。sarX的转录依赖于生长阶段，在生长稳定期表达最高，在mgrA突变体中显著降低。通过转录融合和Northern印迹分析证实，MgrA作为sarX表达的激活剂。凝胶迁移试验表明，纯化的MgrA蛋白与sarX启动子的上游区域结合。用同基因sarX突变体菌株分析了参与毒力和调控的各种潜在靶基因的表达水平，特别是那些受sarA和mgrA影响的基因。我们的数据表明，SarX作为agr位点的阻遏物，从而作为agr系统调控的靶基因的阻遏物。我们提出，SarX是SarA蛋白家族中的一个重要调节因子，可能是agr和sarA基因家族成员控制金黄色葡萄球菌毒力的共同途径的一部分。
