An Escherichia coli ST131 pangenome atlas reveals population structure and evolution across 4,071 isolates
An Escherichia coli ST131 pangenome atlas reveals population structure and evolution across 4,071 isolates
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DOI：
10.1038/s41598-019-54004-5
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发表时间：
2019-11-22
影响因子：
4.6
通讯作者：
Downing, Tim
中科院分区：
文献类型：
--
作者：
Decano, Arun Gonzales;Downing, Tim
大肠杆菌ST 131是广泛的抗生素耐药性（AMR）感染的主要原因，广泛的β-内酰胺类抗生素的使用促进。这种药物压力推动了病原体中超广谱β-内酰胺酶（ESBL）基因的获得和进化，因此必须更清楚地解决ST 131的起源，适应和传播。E.大肠杆菌ST 131的ESBL基因通常嵌入移动的遗传元件（MGE）中，所述MGE有助于转移到新的质粒或染色体位置，所述新的质粒或染色体位置通过质粒接合和重组进一步移动，从而产生具有保守核心基因组的柔性ESBL、MGE和质粒组合物。我们使用群体基因组学，通过提取所有可用的高质量Illumina HiSeq读段文库来更精确地追踪ST 131中AMR的进化，以研究4，071个全球来源的基因组，这是迄今为止研究的最大的ST 131集合。我们应用严格的质量控制、基因组从头组装和ESBL基因筛选来解析ST 131的种群结构，包括三个遗传上不同的进化枝（A、B、C）和来自优势进化枝C的丰富的亚进化枝。我们使用已发表的参考基因组、长读段组装和基于k-mer的方法来构建它们在核心和附属基因组中的进化关系，以使泛基因组多样性背景化。随着时间的推移，三个主要的C亚支以相对稳定的频率在全球范围内共同循环，这表明在它们的起源和最初的快速传播之后达到了平衡。这与它们的ESBL基因形成对比，ESBL基因在时间、地理和亚进化枝上具有更强的模式，并且位于分离株之间的染色体和质粒上的不同位置。在三个C亚分支内，核心和辅助基因组多样性水平由于质粒和MGE活性而不相关，这与三个主要分支A、B和C之间的模式不同。这项群体基因组研究突出了ST 131中附属基因组的动态性质，表明监测应预测具有更广泛抗生素耐药性水平的遗传变异疫情。我们的研究结果强调了进化泛基因组学的潜力，以提高我们对AMR基因转移，适应和传播的理解，以发现与新亚型相关的辅助基因组变化。
Escherichia coli ST131 is a major cause of infection with extensive antimicrobial resistance (AMR) facilitated by widespread beta-lactam antibiotic use. This drug pressure has driven extended-spectrum beta-lactamase (ESBL) gene acquisition and evolution in pathogens, so a clearer resolution of ST131's origin, adaptation and spread is essential. E. coli ST131's ESBL genes are typically embedded in mobile genetic elements (MGEs) that aid transfer to new plasmid or chromosomal locations, which are mobilised further by plasmid conjugation and recombination, resulting in a flexible ESBL, MGE and plasmid composition with a conserved core genome. We used population genomics to trace the evolution of AMR in ST131 more precisely by extracting all available high-quality Illumina HiSeq read libraries to investigate 4,071 globally-sourced genomes, the largest ST131 collection examined so far. We applied rigorous quality-control, genome de novo assembly and ESBL gene screening to resolve ST131's population structure across three genetically distinct Clades (A, B, C) and abundant subclades from the dominant Clade C. We reconstructed their evolutionary relationships across the core and accessory genomes using published reference genomes, long read assemblies and k-mer-based methods to contextualise pangenome diversity. The three main C subclades have co-circulated globally at relatively stable frequencies over time, suggesting attaining an equilibrium after their origin and initial rapid spread. This contrasted with their ESBL genes, which had stronger patterns across time, geography and subclade, and were located at distinct locations across the chromosomes and plasmids between isolates. Within the three C subclades, the core and accessory genome diversity levels were not correlated due to plasmid and MGE activity, unlike patterns between the three main clades, A, B and C. This population genomic study highlights the dynamic nature of the accessory genomes in ST131, suggesting that surveillance should anticipate genetically variable outbreaks with broader antibiotic resistance levels. Our findings emphasise the potential of evolutionary pangenomics to improve our understanding of AMR gene transfer, adaptation and transmission to discover accessory genome changes linked to novel subtypes.