Transmission and microevolution of USA300 MRSA in U.S. households: evidence from whole-genome sequencing.
Transmission and microevolution of USA300 MRSA in U.S. households: evidence from whole-genome sequencing.
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DOI：
10.1128/mbio.00054-15
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发表时间：
2015-03-10
期刊：
影响因子：
6.4
通讯作者：
David MZ
中科院分区：
文献类型：
--
作者：
Alam MT;Read TD;Petit RA 3rd;Boyle-Vavra S;Miller LG;Eells SJ;Daum RS;David MZ
耐甲氧西林金黄色葡萄球菌(MRSA)USA300是美国成功的金黄色葡萄球菌克隆，也是皮肤和软组织感染(SSTI)的常见原因。我们对来自SSTI和定植培养的146株USA300 MRSA分离株进行了全基因组测序(WGS)，这些分离自2008年至2010年在芝加哥和洛杉矶家庭进行的调查，其中包括一例金黄色葡萄球菌SSTI的索引病例。我们鉴定了独特的单核苷酸多态(SNPs)并分析了全基因组系统发育，以确定分离株的特征，以了解USA300 MRSA在家庭中的传播动态、遗传相关性和微进化。我们还将我们研究中的146株USA300 MRSA与之前发表的来自圣地亚哥(n=35)和纽约市(n=277)的USA300 MRSA分离株的基因组序列进行了比较。我们发现来自洛杉矶和芝加哥的USA300MRSA家庭分离株几乎没有遗传变异(平均SNP数±标准差，17.6±35；π核苷酸多样性，3.1×10−5)或芝加哥(平均SNP数±标准差，12±19；π核苷酸多样性，3.1×10−5)。一个家庭内的分离株聚为紧密相关的单系类群，表明单个共同的USA300祖先株引入每个家庭并在每个家庭内传播。从贝叶斯进化重建，我们推断，在抽样之前，USA300在家庭中持续了2.33到8.35年。我们还注意到，对氟喹诺酮耐药的USA300克隆在1995年左右出现，在洛杉矶和纽约市比在芝加哥更普遍。我们的发现强烈表明，独特的USA300 MRSA分离株在包含患有SSTI的个人的家庭中传播。家庭成员的非殖民化可能是控制USA300 MRSA在美国传播的预防计划的关键组成部分。USA300是一种毒力强且易传播的耐甲氧西林金黄色葡萄球菌(MRSA)菌株，是美国主要的社区相关MRSA克隆。它最常见的原因是皮肤感染，但也会引起坏死性肺炎和心内膜炎。只有当我们了解最常见的传播源和为耐甲氧西林金黄色葡萄球菌提供适应优势的微进化过程时，限制耐甲氧西林金黄色葡萄球菌在社区中传播的战略才能有效。我们对来自芝加哥和洛杉矶的146株USA300 MRSA分离株进行了全基因组序列比较。我们表明，家庭是USA300毒株的频繁传播地点和长期储存库；家庭内的个人在彼此之间传播相同的USA300毒株。我们的研究还显示，测序的USA300分离株中有很大一部分对氟喹诺酮类抗生素具有耐药性。这项研究的意义在于，如果家庭作为USA300的长期储备者，家庭MRSA根除计划可能会产生一种独特有效的控制方法。
Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is a successful S. aureus clone in the United States and a common cause of skin and soft tissue infections (SSTIs). We performed whole-genome sequencing (WGS) of 146 USA300 MRSA isolates from SSTIs and colonization cultures obtained from an investigation conducted from 2008 to 2010 in Chicago and Los Angeles households that included an index case with an S. aureus SSTI. Identifying unique single nucleotide polymorphisms (SNPs) and analyzing whole-genome phylogeny, we characterized isolates to understand transmission dynamics, genetic relatedness, and microevolution of USA300 MRSA within the households. We also compared the 146 USA300 MRSA isolates from our study with the previously published genome sequences of the USA300 MRSA isolates from San Diego (n = 35) and New York City (n = 277). We found little genetic variation within the USA300 MRSA household isolates from Los Angeles (mean number of SNPs ± standard deviation, 17.6 ± 35; π nucleotide diversity, 3.1 × 10−5) or from Chicago (mean number of SNPs ± standard deviation, 12 ± 19; π nucleotide diversity, 3.1 × 10−5). The isolates within a household clustered into closely related monophyletic groups, suggesting the introduction into and transmission within each household of a single common USA300 ancestral strain. From a Bayesian evolutionary reconstruction, we inferred that USA300 persisted within households for 2.33 to 8.35 years prior to sampling. We also noted that fluoroquinolone-resistant USA300 clones emerged around 1995 and were more widespread in Los Angeles and New York City than in Chicago. Our findings strongly suggest that unique USA300 MRSA isolates are transmitted within households that contain an individual with an SSTI. Decolonization of household members may be a critical component of prevention programs to control USA300 MRSA spread in the United States. USA300, a virulent and easily transmissible strain of methicillin-resistant Staphylococcus aureus (MRSA), is the predominant community-associated MRSA clone in the United States. It most commonly causes skin infections but also causes necrotizing pneumonia and endocarditis. Strategies to limit the spread of MRSA in the community can only be effective if we understand the most common sources of transmission and the microevolutionary processes that provide a fitness advantage to MRSA. We performed a whole-genome sequence comparison of 146 USA300 MRSA isolates from Chicago and Los Angeles. We show that households represent a frequent site of transmission and a long-term reservoir of USA300 strains; individuals within households transmit the same USA300 strain among themselves. Our study also reveals that a large proportion of the USA300 isolates sequenced are resistant to fluoroquinolone antibiotics. The significance of this study is that if households serve as long-term reservoirs of USA300, household MRSA eradication programs may result in a uniquely effective control method.