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

点击翻译按钮获取中文摘要

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.