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

描述（由申请人提供）由社区中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，一个S。金黄色葡萄球菌流行性克隆USA300是这些感染中绝大多数的原因。虽然USA300的快速传播是有据可查的，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干预措施至关重要，这些干预措施可以有效地防止这些流行性克隆在人群中的传播。我们最近在北方曼哈顿进行了一项NIH资助的MRSA传播病例对照研究。这项研究的一个主要限制是我们无法追踪社区传染网络内的传播途径。这部分是由于目前的分子分型技术分辨率差。最近的研究表明，更详细的序列分析，如全基因组测序，通过记录不同菌株的系统发育关系，可以提供更多关于社区传播途径的信息。本研究的目的是检验全基因组测序作为追踪沙门氏菌传播的工具的效用。金黄色葡萄球菌在社区。为了实现这一目标，我们将利用我们从MRSA传播研究中获得的USA300分离株的良好特征。这些分离株与详细的研究受试者数据库相关联，该数据库包含社会人口统计学、医学和沙门氏菌。金黄色葡萄球菌危险因素信息。全基因组测序区分菌株的能力，从而帮助确定这些菌株如何传播，将与目前可用的技术进行比较。基于基因组序列，将组装USA300分离株的系统发育树，并将作为许多不同比较的基础。主要结局指标将是系统发育树上分离株的接近度。比较将包括分离株的来源（例如，定植、感染、环境）、分离株的空间位置、分离株的基因型。 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见解，并可能成为这些类型的调查的标准方法。USA300收集的可用性加上广泛的研究受试者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.