A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic.
A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic.
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DOI：
10.1101/gr.147710.112
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发表时间：
2013-04
期刊：
影响因子：
7
通讯作者：
Nübel U
中科院分区：
文献类型：
--
作者：
Holden MT;Hsu LY;Kurt K;Weinert LA;Mather AE;Harris SR;Strommenger B;Layer F;Witte W;de Lencastre H;Skov R;Westh H;Zemlicková H;Coombs G;Kearns AM;Hill RL;Edgeworth J;Gould I;Gant V;Cooke J;Edwards GF;McAdam PR;Templeton KE;McCann A;Zhou Z;Castillo-Ramírez S;Feil EJ;Hudson LO;Enright MC;Balloux F;Aanensen DM;Spratt BG;Fitzgerald JR;Parkhill J;Achtman M;Bentley SD;Nübel U
抗生素的广泛使用与高密度的临床护理相结合，推动了耐药细菌的出现，这些细菌适合在住院患者中茁壮成长。特别令人关注的是全球传播的耐甲氧西林金黄色葡萄球菌(MRSA)克隆，它们会导致与卫生保健相关的暴发和流行。目前在欧洲传播最快、最顽强的与医疗保健相关的克隆是EMRSA-15，它于20世纪90年代初在英国首次发现，随后传播到整个欧洲和更远的地方。使用系统基因组学方法分析193株金黄色葡萄球菌的基因组序列，我们能够表明，目前EMRSA-15的大流行群体是20世纪80年代在英格兰蔓延的与医疗保健相关的MRSA流行病的后代，该流行病本身以前是由主要与社区相关的甲氧西林敏感种群产生的。20世纪80年代中期，在英格兰中部地区的这个EMRSA-15亚克隆中出现的氟喹诺酮耐药性似乎在引发大流行传播中发挥了关键作用，并发生在该药物的第一次临床试验后不久。基于基因组的合并分析估计，在过去的20年里，这个亚克隆的种群增长速度是其祖先的四倍。通过比较基因组分析，我们确定了99.8%的分离株耐药表型的分子遗传学基础，突出了病原菌基因组测序作为诊断工具的潜力。我们记录了与适应医院环境和随着时间的推移不断增加的耐药性相关的基因变化，以及MRSA的演变可能如何受到国家特定药物使用方案的影响。
The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.
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DOI：
10.1016/j.cub.2011.05.058
发表时间：
2011-08-09
期刊：
Current biology : CB
影响因子：
--
作者：
Edwards CJ;Suchard MA;Lemey P;Welch JJ;Barnes I;Fulton TL;Barnett R;O'Connell TC;Coxon P;Monaghan N;Valdiosera CE;Lorenzen ED;Willerslev E;Baryshnikov GF;Rambaut A;Thomas MG;Bradley DG;Shapiro B
通讯作者：
Shapiro B
影响因子：
10.7
作者：
Drummond, Alexei J.;Suchard, Marc A.;Rambaut, Andrew
通讯作者：
Rambaut, Andrew
影响因子：
3.2
作者：
CLEWELL, DB;AN, FY;GAWRONBURKE, C
通讯作者：
GAWRONBURKE, C
影响因子：
5.8
作者：
Carver, TJ;Rutherford, KM;Parkhill, J
通讯作者：
Parkhill, J
影响因子：
2.9
作者：
Eyre DW;Golubchik T;Gordon NC;Bowden R;Piazza P;Batty EM;Ip CL;Wilson DJ;Didelot X;O'Connor L;Lay R;Buck D;Kearns AM;Shaw A;Paul J;Wilcox MH;Donnelly PJ;Peto TE;Walker AS;Crook DW
通讯作者：
Crook DW