Global regulation by mgr in S. aureus

性状（由申请人提供）：金黄色葡萄球菌能够引起多种人类疾病。最近由于生物体对抗生素治疗的抗性增加，它变得更加成问题。因此，迫切需要新的治疗方法。这种微生物的致病性可归因于其产生大量细胞表面相关和细胞外毒力因子的能力。这些毒力决定因子由几个不相关的全局调控基因座协同调控。最近，我们已经确定了一个新的基因座，mgr，它影响生产的几个毒力因子的模式不同于其他系统的报告日期。我们随后采用遗传和分子方法来定位和克隆这个全球性的调控位点。测序、基因特异性突变和互补证实该位点为一个新位点。我们的数据还表明，mgrA是最有可能的唯一的基因在这个位点的调控是必需的。在这个提议中，我们提出了三个具体的目标：（i）通过研究转录组织和分析的mgrA基因的启动子区的分子特征的mgr位点;（ii）调查的机制，通过mgr的靶基因调控和识别其他靶基因的微阵列技术;（iii）研究与其他全球监管系统和控制mgrA基因表达的相互作用。将采用各种遗传、生物化学和分子方法来实现这些目标。本提案中概述的研究的成功完成将为经理监管体系提供进一步的见解。这些新的认识无疑将有助于我们对S.金黄色葡萄球菌，这将进一步为开发新的治疗方法提供坚实的基础。

DESCRIPTION (provided by applicant): Staphylococcus aureus is capable of causing a wide range of human diseases. It has become more problematic recently due to increasing resistance of the organism to antibiotic treatment. New methods of treatment are therefore urgently needed. The pathogenicity of this organism could be attributed to its ability to produce a large number of cell surface-associated and extracellular virulence factors. These virulence determinants are coordinately regulated by several unlinked global regulatory loci. Recently, we have identified a novel locus, mgr, which affects the production of several virulence factors in a pattern distinct from other systems reported to date. We have subsequently employed genetic and molecular methods to map and clone this global regulatory locus. Sequencing, gene-specific mutation and complementation confirmed that the mgr was a novel locus. Our data also suggest that mgrA is most likely the only gene in this locus that is required in the regulation. In this proposal, we propose to accomplish three specific aims: (i) to molecularly characterize the mgr locus by studying the transcriptional organization and analyzing the promoter region of the mgrA gene; (ii) to investigate the mechanism of target gene regulation by mgr and to identify additional target genes by micorarray technology; (iii) to study interaction with other global regulatory systems and control of mgrA gene expression. Various genetic, biochemical and molecular approaches will be employed to accomplish these aims. The successful completion of the studies outlined in this proposal will provide further insights into the mgr regulatory system. The new knowledge will undoubtedly contribute to our understanding of global regulatory mechanism in S. aureus, which will further provide a solid basis for the development of new treatments.