摘要

耐甲氧西林金黄色葡萄球菌（MRSA）菌株携带mecA或mecC介导的对β-内酰胺抗生素的抗性机制，并且抗性的表型表现显示广泛的菌株与菌株的变异。在最近的通讯中，我们确定了与严格应激反应相关的遗传决定因素，这些遗传决定因素在历史上最早的“古老”MRSA克隆的抗生素抗性表型和携带MRSA菌株LGA251的mecC中发挥重要作用。在这里，我们试图测试相同的遗传决定因素是否也对主要当代MRSA克隆USA300的高度和均匀抗性（H * R）衍生物的抗性表型起作用。我们发现抗性表型与6个基因（fruB，gmk，hpt，purB，prsA和relA）相关，这些基因在分析的20个H * Rs中最常被靶向（20个H中的19个每个克隆一个突变* RS）。除了与我们先前的发现（匹配的六个基因中的五个）强烈相似之外，发现除了一个重复靶向的基因外，所有基因都与鸟嘌呤代谢相关，表明该途径在确定抗生素抗性水平中起关键作用独立于MRSA的克隆类型。

Methicillin-resistant Staphylococcus aureus (MRSA) strains carry either a mecA- or a mecC-mediated mechanism of resistanceto beta-lactam antibiotics and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications we identified genetic determinants associated with the stringent stress response that play a major role in theantibiotic resistant phenotype of the historically earliest "archaic" clone of MRSA and in the mecC carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone USA300. We found that the resistancephenotype was linked to six genes (fruB, gmk, hpt, purB, prsA, and relA), which were most frequently targeted among the analyzed 20 H*Rs (one mutation per clone in 19 out of the 20 H*Rs). Besides the strong parallels with our previous findings (five out of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA.

https://www.ncbi.nlm.nih.gov/pubmed/29555636