ROLE OF SAER/S DURING S AUREUS PATHOGENESIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 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。 金黄色葡萄球菌(S.金黄色葡萄球菌）是全世界人类感染的主要原因，并引起严重程度从轻度到危及生命的各种疾病。 S.金黄色葡萄球菌引起疾病的部分原因是其破坏先天免疫系统的能力。 最近的研究表明S.金黄色葡萄球菌逃避人多形核白细胞（PMN或嗜中性白细胞）的杀伤。 然而，关于病原体如何检测先天免疫系统的成分以在宿主中应答和存活的了解相对较少。 因此，本研究的长期目标是更好地了解S。金黄色葡萄球菌致病性。 具体的假设是S。金黄色葡萄球菌2  组分基因调控系统saeR/S促进了S.因此对发病机制很重要。迄今为止，Voyich博士的实验室已经在S.金黄色葡萄球菌菌株MW 2（脉冲场型USA 400）。 在PMN相互作用过程中，saeR/S突变体逃避人PMN杀伤的能力大大减弱。 寡核苷酸微阵列分析表明，saeR/S对S.金黄色葡萄球菌毒力在小鼠菌血症模型中，saeR/S缺失显著减弱了葡萄球菌毒力。 相反，他们发现MW 2和突变saeR/S株引起脓肿形成的能力没有显著差异。 总之，saeR/S在PMNs逃避杀伤中起重要作用，并且似乎是S期赋予毒力的关键因子。金黄色葡萄球菌菌血症

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. Staphylococcus aureus (S. aureus) is a leading cause of human infections worldwide and causes a variety of diseases ranging in severity from mild to life-threatening. The ability of S. aureus to cause disease is based in part on its ability to subvert the innate immune system. Recent studies suggest S. aureus evades killing by human polymorphonuclear leukocytes (PMNs or neutrophils). However, relatively little is known about how pathogens detect components of the innate immune system to respond and survive within the host. Therefore, the long term goal of this study is to gain a better understanding of S. aureus pathogenesis. The specific hypothesis is that the S. aureus two  component gene regulatory systems saeR/S facilitates evasion of innate host defenses by S. aureus and is therefore important for pathogenesis. To date Dr. Voyich's lab has generated an isogenic saeR/S deletion mutant in S. aureus strain MW2 (pulse-field type USA400). During PMN interaction the saeR/S mutant was greatly attenuated in its ability to evade killing by human PMNs. Oligonucleotide microarrays indicate saeR/S influences a significant amount of genes of the S. aureus virulon. Deletion of saeR/S significantly attenuated staphylococcal virulence in a mouse model of bacteremia. In contrast, they saw no significant differences in ability between MW2 and the mutant saeR/S strain to cause abscess formation. In summary, saeR/S plays an important role in evasion of killing by PMNs and appears to be a critical factor conferring virulence during S. aureus bacteremia.