MT VET COBRE PROJECT 2: METAL UPTAKE AND REGULATION IN STREPTOCOCCUS PYOGENES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。化脓性链球菌或A群链球菌（GAS）是一种主要的人类病原体，可引起咽炎、链球菌中毒性休克综合征、坏死性筋膜炎、急性风湿热、肾小球肾炎等多种疾病。许多细菌病原体的金属获取系统是毒力因子和有吸引力的免疫治疗靶点。GAS包含三个ABC金属采集转运体，即HtsABC、FtsABCD和MtsABC。该项目的目标是破译必需金属离子在GAS中的获取过程，包括获取机制、调节和对发病机制的影响。通过生化和遗传方法发现FtsABCD对铁铬有吸附作用。雷博士的研究小组发现，金属调节因子MtsR对MtsABC和HtsABC的表达有不同的调节作用。作为该项目的延伸，他们发现了几个对人类血液和小鼠中GAS生长至关重要的基因。他们计划比较这三种转运体对小鼠体内GAS毒力的相对重要性，并描述对GAS在体内生长和存活至关重要的基因。该研究将促进我们对GAS发病机制的认识，并可能找到针对GAS感染的新疫苗和治疗靶点。

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. Streptococcus pyogenes or Group A Streptococcus (GAS) is a major human pathogen causing a variety of diseases, including pharyngitis, streptococcal toxic shock syndrome, necrotizing fasciitis, acute rheumatic fever, and glomerulonephritis. Metal acquisition systems of many bacterial pathogens are virulence factors and attractive immunotherapeutic targets. GAS contains three ABC metal acquisition transporters, namely, HtsABC, FtsABCD, and MtsABC. The objective of this project is to decipher the acquisition processes of essential metal ions in GAS with respect to the acquisition machinery, regulation, and impacts on pathogenesis. FtsABCD has been found to take up ferric ferrichrome by biochemical and genetic methods. Dr. Lei's group found that MtsR, a metalloregulator, differentially regulates the expression of MtsABC and HtsABC. As an extension of this project, they found several genes that are critical for the growth of GAS in human blood and in mice. They plan to compare the relative importance of the three transporters to GAS virulence in mice and to characterize the genes that are critical for in vivo growth and survival of GAS. The study will advance our understanding of GAS pathogenesis and may identify novel vaccine and therapeutic targets against GAS infection.