The use of whole genome sequencing to identify spread of USA300 in the community

描述(申请人提供)由来自社区的耐甲氧西林金黄色葡萄球菌(MRSA)引起的感染急剧增加。在美国，金黄色葡萄球菌流行克隆USA300是造成这些感染的绝大多数原因。虽然USA300的S快速传播有很好的文献记载，但很少有研究调查其显著传播性的基础。克服这一知识差距对于设计能够有效防止这些流行病克隆在人口一级传播的干预措施至关重要。我们最近对曼哈顿北部地区的MRSA传播进行了一项由美国国立卫生研究院资助的病例对照研究。这项研究的一个主要局限性是我们无法追踪社区中感染网络内的传播途径。这在一定程度上是由于目前的分子分型技术分辨率不高。最近的研究表明，更详细的序列分析，如全基因组测序提供的分析，通过记录不同菌株之间的系统发育关系，可以提供关于社区传播途径的更多信息。这项研究的目的是测试全基因组测序作为追踪金黄色葡萄球菌在社区中传播的工具的实用性。为了实现这一目标，我们将利用我们从MRSA传播研究中收集的具有良好特性的USA300分离株。这些分离株与详细的研究对象数据库相关联，该数据库包含社会人口学、医学和金黄色葡萄球菌风险因素信息。全基因组测序区分不同菌株的能力，从而帮助确定这些菌株是如何传播的，将与目前可用的技术进行比较。根据基因组序列，USA300分离株将组成系统发育树，并将作为许多不同比较的基础。主要的结果衡量标准将是分离株在系统发育树上的接近程度。比较将包括分离株的来源(例如，定居、感染、环境)、 菌株分离以及是否可以识别以前未检测到的传播途径。全基因组测序有可能为这种非常成功的克隆的戏剧性出现提供独特的洞察力，并可能成为这些类型研究的标准方法。USA300收藏品的可获得性以及广泛的研究对象数据为解决这一问题提供了独特的机会。

DESCRIPTION (provided by applicant) There has been a dramatic increase in infections caused by methicillin-resistant Staphylococcus aureus (MRSA) that originate in the community. In the United States, a single S. aureus epidemic clone, USA300, has been responsible for the vast majority of these infections. Although USA300's rapid spread is well documented, few studies have investigated the basis for its remarkable transmissibility. Overcoming this gap in knowledge is critical to the design of interventions that can effectively prevent dissemination of these epidemic clones at the population level. We recently conducted an NIH funded, case-control study of MRSA transmission in Northern Manhattan. A major limitation of this study was our inability to trace transmission pathways within infectious networks in the community. This was in part due to the poor resolution of current molecular typing techniques. Recent studies suggest that more detailed sequence analysis, such as that provided by whole genome sequencing, by documenting the phylogenetic relationship of different strains, can provide far greater information on paths of transmission in the community. The goal of this study is to test the utility of whole genome sequencing as a tool to trace the spread of S. aureus in the community. To accomplish this goal we will utilize our well-characterized collection of USA300 isolates from the MRSA transmission study. These isolates are linked to the detailed study subject database that contains sociodemographic, medical and S. aureus risk factor information. The ability of whole genome sequencing to discriminate among strains and as a result to help identify how these strains spread will be compared with the currently available techniques. Based on the genome sequence, a phylogenetic tree will be assembled of the USA300 isolates and will serve as the basis for a number of different comparisons. The primary outcome measure will be the proximity of isolates on the phylogenetic tree. The comparisons will include the source of the isolates (e.g. colonization, infection, environment), the spatial location of the strain isolation and whether previously undetected transmission pathways can be identified. Whole genome sequencing has the potential to provide unique insight into the basis for the dramatic emergence of this highly successful clone, and perhaps become the standard approach for these types of investigations. The availability of the USA300 collection coupled with the extensive study subject data provides a unique opportunity to address this question.