Systems for studying the mobility of the SCCmec element in MRSA

描述（由申请人提供）：这项工作将为长期项目奠定基础，以在分子水平上了解SCCmec元件的移动性，该元件使金黄色葡萄球菌对多种青霉素具有耐药性。产生的MRSA（耐甲氧西林S.金黄色葡萄球菌）菌株已经成为严重的公共卫生问题。该项目将Rice团队在DNA重组酶的结构生物学和生物化学方面的专业知识与Daum和Boyle-Vavra博士的专业知识相结合，Daum和Boyle-Vavra博士是SCCmec架构以及分子流行病学，抗生素耐药性机制和MRSA毒力的专家。该R21的具体目标是：1）开发用于研究具有纯化组分的SCCmec编码的DNA重组酶的体外系统。（2）建立研究S. aureus和E.大肠杆菌染色。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，并设计方法来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。 公共卫生相关性：这项工作将为一个长期项目奠定基础，以了解在分子水平上，SCCmec元素的流动性，使金黄色葡萄球菌耐多种青霉素。将SCCmec DNA元件插入S.金黄色葡萄球菌染色体导致“MRSA”（耐甲氧西林的S.金黄色葡萄球菌）菌株已经成为严重的公共卫生问题。我们对催化这种DNA重组反应的蛋白质的研究将有助于我们了解SCCmec在葡萄球菌属物种之间的传播，并将为设计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奠定基础。

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.