Targeted IS-element sequencing uncovers transposition dynamics during selective pressure in enterococci.
Targeted IS-element sequencing uncovers transposition dynamics during selective pressure in enterococci.
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DOI：
10.1371/journal.ppat.1011424
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发表时间：
2023-06
期刊：
影响因子：
6.7
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中科院分区：
文献类型：
--
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插入序列（IS）是一种简单的转座子，参与了多种病原菌的基因组进化。肠球菌已成为重要的人类肠道病原体，具有新的适应性毒力潜力和抗生素耐药性。这些遗传特征与由移动的元件介导的大规模基因组进化串联出现。肠球菌的病理适应被认为部分由IS元件IS 256通过基因失活和重组事件介导。然而，IS 256的调节和控制其激活的机制还不清楚。在这里，我们采用IS 256特异性深度测序方法来描述慢性裂解性噬菌体感染如何驱动大肠杆菌中IS 256的广泛多样化。faecalis以及抗生素暴露如何与E.临床人类感染期间的粪便。我们通过比较基因组学表明，IS 256主要存在于医院适应性肠球菌分离株中。对IS 256转座酶基因水平的分析表明，在大肠杆菌中，IS 256转座酶在转录水平上受到多种机制的调控。faecalis，表明在没有选择性压力的情况下对IS 256活化的严格控制。我们的研究结果表明，压力源，如抗生素和抗生素暴露驱动快速基因组规模的肠球菌易位。因此，IS 256多样化可以解释选择压力如何介导肠球菌基因组的进化，最终导致威胁人类健康的优势医院谱系的出现。插入序列（IS）元件是细菌中普遍存在的简单转座子。在肠球菌中，包括医学相关的物种，如粪肠球菌和屎肠球菌，IS元件IS 256是广泛存在的，并已涉及发病机制和抗生素耐药性。尽管IS 256对肠球菌生物学的重要性，但我们对该元件如何调节和多样化肠球菌基因组知之甚少。在这里，我们表明，IS 256是优先发现医院适应和强毒菌株的肠球菌。在大肠粪肠球菌V583是一种万古霉素抗性血液分离株，IS 256受多种转录机制调控。为了了解IS 256是如何被动员的，我们采用了一种基于Illumina的深度测序方法，称为IS-Seq，以在施加噬菌体（噬菌体）捕食的选择性压力时发现新的IS 256插入。我们发现，慢性噬菌体感染驱动了E. faecalis V583基因组。此外，我们跟踪了IS 256在人大肠杆菌中的插入活性。粪便感染，并发现增加的IS 256多样性与特定抗生素的使用有关。总之，我们的研究结果表明，肠球菌控制IS 256活性以使其基因组多样化，这可能导致出现威胁人类健康的医院适应菌株。
Insertion sequences (IS) are simple transposons implicated in the genome evolution of diverse pathogenic bacterial species. Enterococci have emerged as important human intestinal pathogens with newly adapted virulence potential and antibiotic resistance. These genetic features arose in tandem with large-scale genome evolution mediated by mobile elements. Pathoadaptation in enterococci is thought to be mediated in part by the IS element IS256 through gene inactivation and recombination events. However, the regulation of IS256 and the mechanisms controlling its activation are not well understood. Here, we adapt an IS256-specfic deep sequencing method to describe how chronic lytic phage infection drives widespread diversification of IS256 in E. faecalis and how antibiotic exposure is associated with IS256 diversification in E. faecium during a clinical human infection. We show through comparative genomics that IS256 is primarily found in hospital-adapted enterococcal isolates. Analyses of IS256 transposase gene levels reveal that IS256 mobility is regulated at the transcriptional level by multiple mechanisms in E. faecalis, indicating tight control of IS256 activation in the absence of selective pressure. Our findings reveal that stressors such as phages and antibiotic exposure drives rapid genome-scale transposition in the enterococci. IS256 diversification can therefore explain how selective pressures mediate evolution of the enterococcal genome, ultimately leading to the emergence of dominant nosocomial lineages that threaten human health. Insertion sequence (IS) elements are simple transposons that are ubiquitous in bacteria. In enterococci, which includes medically relevant species such as Enterococcus faecalis and Enterococcus faecium, the IS element IS256 is widespread and has been implicated in pathogenesis and antibiotic resistance. Despite the importance of IS256 to the biology of enterococci, we know little about how this element is regulated and diversifies enterococcal genomes. Here, we show that IS256 is preferentially found in hospital-adapted and virulent strains of enterococci. In E. faecalis V583, a vancomycin resistant blood isolate, IS256 is regulated by multiple transcriptional mechanisms. To understand how IS256 is mobilized, we adapted an Illumina-based deep sequencing method called IS-Seq to find novel IS256 insertions when applying the selective pressure of bacteriophage (phage) predation. We found that chronic phage infection drives IS256 diversification of the E. faecalis V583 genome. Additionally, we tracked IS256 insertional activity during a human E. faecium infection and found that increased IS256 diversity was associated with specific antibiotic use. Together, our results demonstrate that enterococci control IS256 activity to diversify their genomes which may lead to the emergence of hospital-adapted strains that threaten human health.
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