Sequential Acquisition of Virulence and Fluoroquinolone Resistance Has Shaped the Evolution of Escherichia coli ST131.
Sequential Acquisition of Virulence and Fluoroquinolone Resistance Has Shaped the Evolution of Escherichia coli ST131.
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DOI：
10.1128/mbio.00347-16
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发表时间：
2016-04-26
期刊：
影响因子：
6.4
通讯作者：
Beatson SA
中科院分区：
文献类型：
--
作者：
Ben Zakour NL;Alsheikh-Hussain AS;Ashcroft MM;Khanh Nhu NT;Roberts LW;Stanton-Cook M;Schembri MA;Beatson SA
大肠杆菌ST131是世界范围内分离最频繁的氟喹诺酮耐药(FQR)大肠杆菌克隆，是尿路和血液感染的主要原因。虽然最初是通过与CTX-M-15超广谱β-内酰胺酶耐药基因的关联来鉴定，但全球基因组流行病学研究未能解决ST131祖先的地理和时间起源。在这里，我们开发了一个框架，用于重新分析来自不同国家的公开可用基因组，并使用该数据集重建导致FQR ST131出现的进化步骤。使用贝叶斯估计，我们证明了导致FQR的染色体基因点突变与1986年首次临床使用氟喹诺酮类药物一致，并说明了这一关键事件对ST131从明显起源于北美的全球人口快速扩张的影响。此外，我们发现了在FQR发生之前的毒力因子获得事件，这表明毒力相关基因的获得随后是抗生素耐药性的串联发展启动了ST131的成功全球传播。大肠埃希菌131型序列(ST131)是新近出现的一种全球传播的多药耐药克隆，常与人类尿路和血液感染有关。在这项研究中，我们使用了两个公共可用的大型基因组数据集来定义这种重要病原体进化的一些关键步骤。我们发现，氟喹诺酮类抗生素是一种在人类医学和兽医实践中广泛使用的广谱抗生素，在美国引入这些抗生素后不久，ST131就产生了耐药性，很可能是在北美。我们还绘制了ST131获得几个适合度和毒力决定因素的图谱，并证明这些事件发生在氟喹诺酮耐药之前。因此，ST131病毒悄悄地出现了，首先获得了与导致人类感染能力增强相关的基因，然后获得了一种抵抗力武器，推动了它在全球的大规模人口扩张。
Escherichia coli ST131 is the most frequently isolated fluoroquinolone-resistant (FQR) E. coli clone worldwide and a major cause of urinary tract and bloodstream infections. Although originally identified through its association with the CTX-M-15 extended-spectrum β-lactamase resistance gene, global genomic epidemiology studies have failed to resolve the geographical and temporal origin of the ST131 ancestor. Here, we developed a framework for the reanalysis of publically available genomes from different countries and used this data set to reconstruct the evolutionary steps that led to the emergence of FQR ST131. Using Bayesian estimation, we show that point mutations in chromosomal genes that confer FQR coincide with the first clinical use of fluoroquinolone in 1986 and illustrate the impact of this pivotal event on the rapid population expansion of ST131 worldwide from an apparent origin in North America. Furthermore, we identify virulence factor acquisition events that predate the development of FQR, suggesting that the gain of virulence-associated genes followed by the tandem development of antibiotic resistance primed the successful global dissemination of ST131. Escherichia coli sequence type 131 (ST131) is a recently emerged and globally disseminated multidrug-resistant clone frequently associated with human urinary tract and bloodstream infections. In this study, we have used two large publically available genomic data sets to define a number of critical steps in the evolution of this important pathogen. We show that resistance to fluoroquinolones, a class of broad-spectrum antibiotic used extensively in human medicine and veterinary practice, developed in ST131 soon after the introduction of these antibiotics in the United States, most likely in North America. We also mapped the acquisition of several fitness and virulence determinants by ST131 and demonstrate these events occurred prior to the development of fluoroquinolone resistance. Thus, ST131 has emerged by stealth, first acquiring genes associated with an increased capacity to cause human infection, and then gaining a resistance armory that has driven its massive population expansion across the globe.