THE SAER/S SYSTEM OF S AUREUS: SENSING AND RESPONDING TO INNATE IMMUNITY

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 博士Voyich研究了SaeR/S双组分系统（TCS）在USA 300中的作用，USA 300是社区相关耐甲氧西林（CA-MRSA）金黄色葡萄球菌的一种致病循环克隆。 利用USA 300的saeR/S等基因缺失突变体（USA 300SaeR/S），Voyich博士已经证明，在浅表和侵入性感染期间，这种感觉系统对USA 300的发病机制至关重要。 寡核苷酸芯片和真实的时间RT-PCR鉴定了USA 300中大量下调的细胞外毒力基因saeR/S参与宿主细胞裂解、宿主免疫应答的操纵以及与宿主蛋白的粘附。 5 '-RACE分析鉴定了对受SaeR/S强烈影响的基因启动子特异的SaeR识别序列（SRS），并且凝胶位移证明纯化的重组SaeR与启动子序列的结合对应于该序列内SRS的数目。 这项研究揭示了SaeR/S直接与特定毒力基因启动子内的保守共有序列相互作用，从而显著影响USA 300的发病机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dr. Voyich has investigated the role of the SaeR/S two-component system (TCS) in USA300, a prominant circulating clone of community-associated methicillin resistant (CA-MRSA) Staphylococcus aureus. Using an saeR/S isogenic deletion mutant of USA300 (USA300saeR/S) in murine models of sepsis and soft tissue infection, Dr. Voyich has demonstrated this sensory system is critical to USA300 pathogenesis during both superficial and invasive infection. Oligonucleotide microarray and real time RT-PCR identified numerous extracellular virulence genes downregulated in USA300saeR/S involved with host cell lysis, manipulation of the host immune response, and adhesion to host proteins. 5'-RACE analysis identified an SaeR recognition sequence (SRS) specific to gene promoters strongly influenced by SaeR/S, and gel shifts demonstrated the binding of purified recombinant SaeR to promoter sequences corresponded to the number of SRSs within that sequence. This investigation reveals SaeR/S directly interacts with a conserved consensus sequence within specific virulence gene promoters to substantially influence the pathogenesis of USA300.