Systems for studying the mobility of the SCCmec element in MRSA

描述（由申请人提供）：这项工作将为一个长期项目奠定基础，该项目将在分子水平上了解SCCmec元素的流动性，该元素使金黄色葡萄球菌对多种青霉素具有耐药性。由此产生的MRSA（耐甲氧西林金黄色葡萄球菌）菌株已成为一个严重的公共卫生问题。这个项目结合了莱斯大学在DNA重组酶的结构生物学和生物化学方面的专业知识。Daum和Boyle-Vavra，他们是SCCmec结构以及MRSA的分子流行病学，抗生素耐药性机制和毒力方面的专家。本R21的具体目的是：1)建立一个体外系统，用于研究具有纯化组分的sccmec编码DNA重组酶。2)建立在金黄色葡萄球菌和大肠杆菌染色剂中研究这些蛋白的体内系统。长期目标是在原子水平上了解这些重组酶的机制和调控，利用这些知识来了解SCCmec的水平传播，并设计出阻止其传播到新菌株和/或触发其从MRSA基因组中切除和丢失的方法。

DESCRIPTION (provided by applicant): This work will lay the foundation for a long-term project to understand, at a molecular level, the mobility of the SCCmec element that renders Staphylococcus aureus resistant to a broad variety of penicillins. The resulting MRSA (methicillin resistant S. aureus) strains have become a serious public health problem. This project combines the Rice group's expertise in the structural biology and biochemistry of DNA recombinases with that of Drs. Daum and Boyle-Vavra, who are experts in SCCmec architecture as well as the molecular epidemiology, antibiotic resistance mechanisms, and virulence of MRSA. The specific aims of this R21 are to: 1) Develop an in vitro system for studying SCCmec-encoded DNA recombinases with purified components. and 2) Develop in vivo systems for studying these proteins in S. aureus and E. coli stains. The long-term goals are to understand the mechanism and regulation of these recombinases at the atomic level, to leverage this knowledge to understand the horizontal transmission of SCCmec, and to devise ways to stop its spread into new strains and/or trigger its excision and loss from the MRSA genome. PUBLIC HEALTH RELEVANCE: This work will lay the foundation for a long-term project to understand, at a molecular level, the mobility of the SCCmec element that renders Staphylococcus aureus resistant to a broad variety of penicillins. Insertion of the SCCmec DNA element into the S. aureus chromosome results in "MRSA" (methicillin resistant S. aureus) strains that have become a serious public health problem. Our study of the proteins that catalyze this DNA recombination reaction will help us understand the transmission of SCCmec between Staphylococcus species, and will lay the groundwork for devising ways to stop its spread into new strains and/or trigger its excision and loss from the MRSA genome.