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传染病的主要原因；这些细菌已经对所有相关类别的抗生素产生抗药性，并已在社区和医疗保健环境中建立。表皮葡萄球菌和其他凝固酶阴性葡萄球菌，曾经被认为是共生物种，现在已经成为与留置医疗器械相关的感染的主要原因。葡萄球菌引起的人类发病率和死亡率很大程度上是由于少数成功的、广泛的克隆造成的。在目前的提案中，我们试图利用快速下一代测序的能力来获得对几种致病葡萄球菌的克隆出现和适应的更完整的视角。具体地说，我们将(1)阐明细微规模的种群结构及其来源， USA300 MRSA克隆的地理传播模式和临床重要特征的演变，以确定持续流行的特征，确定关键变种的生物标记物，并为未来的流行病学干预提供基线数据；(2)验证致病凝固酶阴性物种中的粗略群体结构，以确定致病变种的新生物标记物；(3)比较金黄色葡萄球菌和表皮葡萄球菌全基因组的长期正选择目标，揭示平衡多态对特定的抗菌素耐药性的重要性。

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.