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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Voyich博士研究了SAER/S双组分系统在USA300中的作用，USA300是社区相关甲氧西林耐药(CA-MRSA)金黄色葡萄球菌的重要循环克隆。Voyich博士在脓毒症和软组织感染的小鼠模型中使用了USA300的Saer/S等基因缺失突变体(USA300saeR/S)，证明了这种感觉系统在表面和侵袭性感染中都对USA300的发病至关重要。寡核苷酸芯片和实时荧光定量RT-PCR鉴定了USA300saeR/S中大量下调的胞外毒力基因，这些基因参与了宿主细胞的裂解、宿主免疫反应的调控以及与宿主蛋白的黏附。5‘-RACE分析确定了受SAER/S强烈影响的基因启动子特异的SAER识别序列，凝胶位移表明纯化的重组SAER与启动子序列的结合与序列中SRSS的数量相对应。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识序列相互作用，对USA300的致病机制产生了重大影响。

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.