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

金黄色葡萄球菌的 SAER/S 系统：感知和响应先天免疫

• 批准号: 7721029
• 负责人: Jovanka M Voyich
• 金额: $ 18.64万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721029
• 关键词: Attenuated; Communities; Complex; Computer Retrieval of Information on Scientific Projects Database; Cues; Data; Disease; Environment; Funding; Gene Components; Genes; Goals; Grant; Host Defense; Human; Immune system; Infection; Institution; Life; Natural Immunity; Pathogenesis; Phagocytosis; Physiologic pulse; Pulse taking; Range; Research; Research Personnel; Resources; Sepsis; Signal Transduction; Source; Staphylococcus aureus; System; Transcriptional Regulation; United States National Institutes of Health; Virulence; Virulent; base; mouse model; neutrophil; pathogen; response; skin abscess

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. The highly adaptable pathogen is the causative agent of diverse diseases ranging from superficial skin abscesses to life-threatening diseases. The ability of S. aureus to adapt to varied environments is dependent on complex accessory gene systems, including those involved in virulence/pathogenesis. Expression of these accessory gene systems is tightly controlled by transcriptional regulatory networks, including two-component signal transduction systems. Nevertheless, how the pathogen senses and responds to different environmental cues during invasion of the human host is not well understood. Thus, Dr. Voyich's long-term goal is to gain a better understanding of mechanisms of S. aureus pathogenesis. Dr. Voyich's preliminary studies suggest the ability of S. aureus to cause disease is based in part on its ability to evade our innate immune system. More specifically, S. aureus can avert destruction by one of the most potent effectors of innate immunity, the polymorphonuclear leukocyte (PMN or neutrophil). Based on preliminary findings, Dr. Voyich hypothesizes that the S. aureus two-component regulatory system saeR/S triggers pathogen-protective responses to innate host defense(s). This hypothesis is based on the following key observations: (1) saeR/S was highly up-regulated during PMN phagocytosis (86), (2) deletion of saeR/S in the virulent community-associated strain MW2 (pulse-field type USA 400) significantly attenuated survival during PMN phagocytosis (3) deletion of saeR/S significantly attenuated virulence in a mouse model of sepsis. Collectively, these data suggest that saeR/S is triggered by a PMN component(s) and genes under its influence are necessary for PMN evasion and sepsis.

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。高度适应性的病原体是从浅表皮肤脓肿到危及生命的疾病的多种疾病的病原体。 S.金黄色葡萄球菌对不同环境的适应依赖于复杂的辅助基因系统，包括那些参与毒力/致病性的辅助基因系统。 这些辅助基因系统的表达受到转录调控网络（包括双组分信号转导系统）的紧密控制。 然而，在入侵人类宿主期间，病原体如何感知和响应不同的环境线索还没有很好地了解。 因此，Voyich博士的长期目标是更好地了解S.金黄色葡萄球菌致病性。 沃伊奇博士的初步研究表明，S。金黄色葡萄球菌致病的部分原因是它能够逃避我们的先天免疫系统。 更具体地说，S.金黄色葡萄球菌可以避免先天免疫的最有效的效应物之一，多形核白细胞（PMN或嗜中性粒细胞）的破坏。根据初步的发现，沃伊奇博士推测，S。金黄色葡萄球菌双组分调控系统saeR/S触发病原体对宿主先天防御的保护性应答。 该假设基于以下关键观察结果：（1）在PMN吞噬作用期间，saeR/S高度上调（86），（2）在PMN吞噬作用期间，在强毒群体相关菌株MW 2（脉冲场型USA 400）中缺失saeR/S显著降低存活率（3）在脓毒症小鼠模型中缺失saeR/S显著降低毒力。 总之，这些数据表明，saeR/S是由PMN成分触发的，受其影响的基因是PMN逃逸和脓毒症所必需的。