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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus
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Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus

机译:医院相关耐甲氧西林金黄色葡萄球菌的出现,适应和传播的分子示踪

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摘要

Hospital-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a global health burden dominated by a small number of bacterial clones. The pandemic EMRSA-16 clone (ST36-II) has been widespread in UK hospitals for 20 y, but its evolutionary origin and the molecular basis for its hospital association are unclear. We carried out a Bayesian phylogenetic reconstruction on the basis of the genome sequences of 87 S. aureus isolates including 60 EMRSA-16 and 27 additional clonal complex 30 (CC30) isolates, collected from patients in three continents over a 53-y period. The three major pandemic clones to originate from the CC30 lineage, including phage type 80/81, Southwest Pacific, and EMRSA-16, shared a most recent common ancestor that existed over 100 y ago, whereas the hospital-associated EMRSA-16 clone is estimated to have emerged about 35 y ago. Our CC30 genome-wide analysis revealed striking molecular correlates of hospital- or community-associated pandemics represented by mobile genetic elements and nonsynonymous mutations affecting antibiotic resistance and virulence. Importantly, phylogeographic analysis indicates that EMRSA-16 spread within the United Kingdom by transmission from hospitals in large population centers in London and Glasgow to regional health-care settings, implicating patient referrals as an important cause of nationwide transmission. Taken together, the high-resolution phylogenomic approach used resulted in a unique understanding of the emergence and transmission of a major MRSA clone and provided molecular correlates of its hospital adaptation. Similar approaches for hospital-associated clones of other bacterial pathogens may inform appropriate measures for controlling their intra- and interhospital spread.
机译:由耐甲氧西林的金黄色葡萄球菌(MRSA)引起的医院相关感染是由少数细菌克隆控制的全球健康负担。大流行的EMRSA-16克隆(ST36-II)在英国的医院中已经流行了20年,但是其进化起源和与医院的关联的分子基础尚不清楚。我们基于在53年内从三大洲的患者收集的87株金黄色葡萄球菌分离物的基因组序列,包括60株EMRSA-16和27株其他克隆复合物30(CC30)分离株的基因组序列,进行了贝叶斯系统发育重建。源自CC30谱系的三个主要的大流行克隆包括80/81型噬菌体,西南太平洋和EMRSA-16,它们共享了100多年前的最新共同祖先,而与医院相关的EMRSA-16克隆是估计大约在35年前出现。我们的CC30全基因组分析揭示了医院或社区相关大流行的显着分子相关性,这些分子相关性是由可移动的遗传元件和影响抗生素耐药性和毒性的非同义突变所代表的。重要的是,系统地理分析表明,EMRSA-16通过从伦敦和格拉斯哥人口密集中心的医院传播到区域医疗机构而在英国范围内传播,这意味着患者转诊是全国传播的重要原因。综上所述,所使用的高分辨率系统基因组方法对主要的MRSA克隆的出现和传播产生了独特的理解,并为其医院适应性提供了分子相关性。与医院相关的其他细菌病原体克隆的相似方法可能会为控制其在院内和院际传播中采取适当措施提供信息。

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  • 作者单位

    The Roslin Institute and Edinburgh Infectious Diseases, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian EH259RG, United Kingdom;

    Microbiology, Royal Infirmary of Edinburgh, Edinburgh EH164SA, United Kingdom;

    Scottish MRSA Reference Laboratory, National Health Service Greater Glasgow and Clyde, Stobhill Hospital, Glasgow G213UW, United Kingdom;

    The Wellcome Trust Sanger Institute, Cambridge CB101SA, United Kingdom;

    Department of Biology and Biochemistry, University of Bath, Bath BA27AY, United Kingdom;

    Department of Infectious Disease Epidemiology, Imperial College London, London W21PG, United Kingdom;

    Department of Infectious Disease Epidemiology, Imperial College London, London W21PG, United Kingdom;

    Department of Infectious Disease Epidemiology, Imperial College London, London W21PG, United Kingdom;

    The Wellcome Trust Sanger Institute, Cambridge CB101SA, United Kingdom;

    The Wellcome Trust Sanger Institute, Cambridge CB101SA, United Kingdom;

    AmpliPhi Biosciences Corp., Colworth Science Park, Bedfordshire MK441LQ, United Kingdom;

    The Roslin Institute and Edinburgh Infectious Diseases, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian EH259RG, United Kingdom;

    Scottish MRSA Reference Laboratory, National Health Service Greater Glasgow and Clyde, Stobhill Hospital, Glasgow G213UW, United Kingdom;

    Broad Institute of Massachusetts Institute of Technology and Harvard, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142;

    Broad Institute of Massachusetts Institute of Technology and Harvard, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142;

    Microbiology Services Colindale, Health Protection-Agency, London NW9 5EQ, United Kingdom;

    Institute of Evolutionary Biology, Ashworth Laboratories, University of Edinburgh, Midlothian EH3 9JT, United Kingdom Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, MD 20892;

    Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216;

    The Roslin Institute and Edinburgh Infectious Diseases, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian EH259RG, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    nosocomial; epidemiology;

    机译:医院的流行病学;

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