Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131.
Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131.
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DOI：
10.1128/mbio.02162-15
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发表时间：
2016-03-22
期刊：
影响因子：
6.4
通讯作者：
Modernizing Medical Microbiology Informatics Group (MMMIG)
中科院分区：
文献类型：
--
作者：
Stoesser N;Sheppard AE;Pankhurst L;De Maio N;Moore CE;Sebra R;Turner P;Anson LW;Kasarskis A;Batty EM;Kos V;Wilson DJ;Phetsouvanh R;Wyllie D;Sokurenko E;Manges AR;Johnson TJ;Price LB;Peto TE;Johnson JR;Didelot X;Walker AS;Crook DW;Modernizing Medical Microbiology Informatics Group (MMMIG)
大肠埃希菌131型序列(ST131)已成为临床上最重要的肠外病原菌谱系，其与氟喹诺酮类药物和超广谱头孢菌素耐药的相关性显著影响治疗。这一谱系的进化史，以及其中重要的抗菌素耐药性成分，仍然没有明确的定义。这项对迄今全球最大的ST131大肠杆菌分离株序列测定(n=215)的研究表明，两个先前公认的抗菌素耐药分支C1/H30R和C2/H30Rx的克隆性扩展始于大约25年前，这与氟喹诺酮类药物和超广谱头孢菌素在临床医学中的广泛引入一致。这两个分支似乎出现在美国，C2/H30Rx分支的扩张是由获得含有blaCTX-M-15的IncFII样质粒驱动的，该质粒随后经历了广泛的重排。描述了影响这一耐药谱系轨迹的其他几个进化过程，包括零星获得CTX-M耐药质粒，以及blaCTX-M在亚群内的染色体整合，随后是垂直进化。最近在类似BLACTX-M-14/14组的ST131中观察到的另一类CTX-M基因变异也发生了这些过程。ST131的进化历史的复杂性对耐药性监测、流行病学分析和控制新出现的大肠杆菌临床谱系具有重要意义。这些数据还突显了减少特定抗生素选择压力的全球紧迫性，并证明了质粒和其他可移动遗传元件在谱系内持久存在抗菌素耐药性方面发挥的重要和多样的作用。大肠埃希菌是一种常年的主要细菌病原体，由于对所有首选抗菌素都出现了耐药性，因此管理起来越来越困难。耐药性集中在特定的大肠杆菌谱系中，如序列型131(ST131)。阐明克隆相关抗性的遗传基础是制定干预策略的关键。我们使用对大量全球ST131分离株的高分辨率基因组分析来确定ST131产超广谱β-内酰胺酶的进化历史。我们记录了不同的遗传过程，包括抗性基因的稳定染色体整合，亚系内可移动的抗性元件的持续和进化，以及不同抗性元件的零星获得。全球分布和地区隔离都很明显。ST131中抗性元件获取和繁殖的多样性表明需要针对细菌菌株和可移动遗传元件的控制和监测策略。
Escherichia coli sequence type 131 (ST131) has emerged globally as the most predominant extraintestinal pathogenic lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and of important antimicrobial resistance elements within it, remain unclearly defined. This study of the largest worldwide collection (n = 215) of sequenced ST131 E. coli isolates to date demonstrates that the clonal expansion of two previously recognized antimicrobial-resistant clades, C1/H30R and C2/H30Rx, started around 25 years ago, consistent with the widespread introduction of fluoroquinolones and extended-spectrum cephalosporins in clinical medicine. These two clades appear to have emerged in the United States, with the expansion of the C2/H30Rx clade driven by the acquisition of a blaCTX-M-15-containing IncFII-like plasmid that has subsequently undergone extensive rearrangement. Several other evolutionary processes influencing the trajectory of this drug-resistant lineage are described, including sporadic acquisitions of CTX-M resistance plasmids and chromosomal integration of blaCTX-M within subclusters followed by vertical evolution. These processes are also occurring for another family of CTX-M gene variants more recently observed among ST131, the blaCTX-M-14/14-like group. The complexity of the evolutionary history of ST131 has important implications for antimicrobial resistance surveillance, epidemiological analysis, and control of emerging clinical lineages of E. coli. These data also highlight the global imperative to reduce specific antibiotic selection pressures and demonstrate the important and varied roles played by plasmids and other mobile genetic elements in the perpetuation of antimicrobial resistance within lineages. Escherichia coli, perennially a major bacterial pathogen, is becoming increasingly difficult to manage due to emerging resistance to all preferred antimicrobials. Resistance is concentrated within specific E. coli lineages, such as sequence type 131 (ST131). Clarification of the genetic basis for clonally associated resistance is key to devising intervention strategies. We used high-resolution genomic analysis of a large global collection of ST131 isolates to define the evolutionary history of extended-spectrum beta-lactamase production in ST131. We documented diverse contributory genetic processes, including stable chromosomal integrations of resistance genes, persistence and evolution of mobile resistance elements within sublineages, and sporadic acquisition of different resistance elements. Both global distribution and regional segregation were evident. The diversity of resistance element acquisition and propagation within ST131 indicates a need for control and surveillance strategies that target both bacterial strains and mobile genetic elements.