Origin, maintenance and spread of antibiotic resistance genes within plasmids and chromosomes of bloodstream isolates of Escherichia coli
Origin, maintenance and spread of antibiotic resistance genes within plasmids and chromosomes of bloodstream isolates of Escherichia coli
复制标题
DOI：
10.1099/mgen.0.000353
复制
发表时间：
2020-04-01
影响因子：
3.9
通讯作者：
Evans, Thomas J.
中科院分区：
文献类型：
--
作者：
Goswami, Cosmika;Fox, Stephen;Evans, Thomas J.
在英国和其他地方，大肠杆菌的血流侵入是菌血症的最常见原因，可归因死亡率约为15-20%;对多种药物的抗生素耐药性在这种微生物中很常见，并与更差的结局相关。赋予抗菌素耐药性的基因及其在水平转移的遗传元件上的频繁位置是公认的，但这些决定簇的起源及其在临床相关细菌群体中维持和传播的能力尚不清楚。在此，我们检测了16株血流中分离的大肠杆菌的染色体和质粒中抗菌素耐药基因的分布。从苏格兰患者中分离出的大肠杆菌，以及这些基因是如何维持和传播的。使用短读和长读全基因组测序方法的组合，我们能够组装44个质粒的完整序列，其中16个Inc F组质粒和20个col质粒;抗生素抗性基因几乎完全位于F组内。bla（CTX-M15）基因在一些菌株中仅重排到染色体中（5个菌株），而另一些菌株仅含有质粒拷贝（2个菌株）。含有多个抗生素基因的整合子广泛存在于质粒中，特别是许多具有编码甲氧苄啶抗性的dfrA 7基因，从而将甲氧苄啶抗性与质粒内的其他抗生素抗性基因联系起来。这将允许甚至窄谱抗生素如甲氧苄啶作为含有介导更广泛抗性的抗生素抗性基因的质粒的选择剂，包括blaC（TX-M15）。据我们所知，这是第一个分析，以提供完整的染色体和质粒的序列数据，在收集致病性人类血流分离的大肠杆菌。杆菌我们的研究结果揭示了质粒和整合和接合元件在致病性大肠杆菌内抗生素抗性基因的维持和传播中的相互作用。杆菌
Blood stream invasion by Escherichia coli is the commonest cause of bacteremia in the UK and elsewhere with an attributable mortality of about 15-20%; antibiotic resistance to multiple agents is common in this microbe and is associated with worse outcomes. Genes conferring antimicrobial resistance, and their frequent location on horizontally transferred genetic elements is well-recognised, but the origin of these determinants, and their ability to be maintained and spread within clinically-relevant bacterial populations is unclear. Here, we set out to examine the distribution of antimicrobial resistance genes in chromosomes and plasmids of 16 bloodstream isolates of E. coli from patients within Scotland, and how these genes are maintained and spread. Using a combination of short and long-read whole genome sequencing methods, we were able to assemble complete sequences of 44 plasmids, with 16 Inc group F and 20 col plasmids; antibiotic resistance genes located almost exclusively within the F group. bla(CTX-M15) genes had re-arranged in some strains into the chromosome alone (five strains), while others contained plasmid copies alone (two strains). Integrons containing multiple antibiotic genes were widespread in plasmids, notably many with a dfrA7 gene encoding resistance to trimethoprim, thus linking trimethoprim resistance to the other antibiotic resistance genes within the plasmids. This will allow even narrow spectrum antibiotics such as trimethoprim to act as a selective agent for plasmids containing antibiotic resistance genes mediating much broader resistance, including blaC(TX-M15). To our knowledge, this is the first analysis to provide complete sequence data of chromosomes and plasmids in a collection of pathogenic human bloodstream isolates of E. coli. Our findings reveal the interplay between plasmids and integrative and conjugative elements in the maintenance and spread of antibiotic resistance genes within pathogenic E. coli.