Population Genomics of Staphylococci

描述（由申请人提供）： 耐甲氧西林金黄色葡萄球菌（MRSA）是美国和世界其他地方感染性疾病的主要原因;这些细菌已获得对所有相关类别抗生素的耐药性，并已在社区和医疗保健环境中确立。表皮葡萄球菌和其他凝固酶阴性葡萄球菌，曾经被认为是唯一的细菌种属，已经成为与留置医疗器械相关的感染的主要原因。由葡萄球菌引起的人类发病率和死亡率大部分是由于少数成功的、广泛的克隆。在目前的建议中，我们试图利用快速下一代测序的力量，以获得一个更完整的角度克隆的出现和适应几个致病性葡萄球菌。具体而言，我们将（1）阐明精细规模的人口结构和起源， USA 300 MRSA克隆的地理传播模式和临床重要性状的演变，以表征正在进行的流行病，鉴定关键变体的生物标志物，并为未来的流行病学干预提供基线数据;（2）验证致病性凝固酶阴性物种内的粗规模群体结构，以鉴定致病性变体的新生物标志物;（3）比较S.金黄色葡萄球菌和表皮并揭示平衡多态性对特定抗菌药物耐药性的重要性。

DESCRIPTION (provided by applicant): Methicillin-resistant Staphylococcus aureus (MRSA) are a leading cause of infectious disease in the United States and elsewhere in the world; these bacteria have acquired resistance to all relevant classes of antibiotics and have become established in community and healthcare environments. Staphylococcus epidermidis and other coagulase-negative staphylococci, once exclusively considered to be commensal species, have emerged as a leading cause of infections associated with indwelling medical devices. Much of the human morbidity and mortality caused by staphylococci are due to a small number of successful, widespread clones. In the current proposal, we seek to exploit the power of rapid next-generation sequencing to obtain a more complete perspective of clone emergence and adaptation for several pathogenic staphylococci. Specifically, we will (1) elucidate fine-scale population structure and the origins, patterns of geographic spread, and evolution of clinically important traits of the USA300 MRSA clone, to characterize an ongoing epidemic, identify biomarkers of key variants, and provide baseline data for future epidemiological interventions; (2) validate coarse-scale population structure within pathogenic coagulase-negative species to identify novel biomarkers of pathogenic variants; (3) compare genome-wide targets of long-term positive selection in S. aureus and S. epidermidis and reveal the importance of balanced polymorphisms to specific antimicrobial resistances.