UK Health Security Agency, London, UK.
NIHR Health Protection Research Unit in Genomics and Enabling Data, University of Warwick, Warwick, UK.
Microb Genom. 2024 May;10(5). doi: 10.1099/mgen.0.001247.
Evidence is accumulating in the literature that the horizontal spread of antimicrobial resistance (AMR) genes mediated by bacteriophages and bacteriophage-like plasmid (phage-plasmid) elements is much more common than previously envisioned. For instance, we recently identified and characterized a circular P1-like phage-plasmid harbouring a gene conferring extended-spectrum beta-lactamase (ESBL) resistance in serovar Typhi. As the prevalence and epidemiological relevance of such mechanisms has never been systematically assessed in , in this study we carried out a follow-up retrospective analysis of UK isolates previously sequenced as part of routine surveillance protocols between 2016 and 2021. Using a high-throughput bioinformatics pipeline we screened 47 784 isolates for the presence of the P1 lytic replication gene , identifying 226 positive isolates from 25 serovars and demonstrating that phage-plasmid elements are more frequent than previously thought. The affinity for phage-plasmids appears highly serovar-dependent, with several serovars being more likely hosts than others; most of the positive isolates (170/226) belonged to . Typhimurium ST34 and ST19. The phage-plasmids ranged between 85.8 and 98.2 kb in size, with an average length of 92.1 kb; detailed analysis indicated a high amount of diversity in gene content and genomic architecture. In total, 132 phage-plasmids had the p0111 plasmid replication type, and 94 the IncY type; phylogenetic analysis indicated that both horizontal and vertical gene transmission mechanisms are likely to be involved in phage-plasmid propagation. Finally, phage-plasmids were present in isolates that were resistant and non-resistant to antimicrobials. In addition to providing a first comprehensive view of the presence of phage-plasmids in , our work highlights the need for a better surveillance and understanding of phage-plasmids as AMR carriers, especially through their characterization with long-read sequencing.
文献中不断积累的证据表明,噬菌体和噬菌体样质粒(phage-plasmid)元件介导的抗生素耐药性(AMR)基因的水平传播比以前想象的要普遍得多。例如,我们最近在伤寒血清型 Typhi 中鉴定并表征了一种携带可赋予扩展谱β-内酰胺酶(ESBL)耐药性的 基因的环状 P1 样噬菌体-质粒。由于此类机制的流行程度和流行病学相关性从未在 中系统评估过,因此在这项研究中,我们对 2016 年至 2021 年期间作为常规监测方案的一部分进行测序的英国 分离株进行了后续回顾性分析。我们使用高通量生物信息学管道筛选了 47784 株分离株中是否存在 P1 裂解复制基因 ,从 25 种血清型中鉴定出 226 株阳性分离株,并证明噬菌体-质粒元件比以前认为的更为常见。噬菌体-质粒的亲和力似乎高度依赖于血清型,一些血清型比其他血清型更有可能成为宿主;大多数阳性分离株(226 个中的 170 个)属于 血清型 Typhimurium ST34 和 ST19。噬菌体-质粒的大小在 85.8 到 98.2kb 之间,平均长度为 92.1kb;详细分析表明基因内容和基因组结构存在高度多样性。总共,132 个噬菌体-质粒具有 p0111 质粒复制类型,94 个具有 IncY 类型;系统发育分析表明,水平和垂直基因传递机制都可能参与噬菌体-质粒的传播。最后,在对抗生素耐药和非耐药的分离株中都存在噬菌体-质粒。除了首次全面了解 中噬菌体-质粒的存在情况外,我们的工作还强调了需要更好地监测和了解噬菌体-质粒作为 AMR 载体的情况,特别是通过长读测序对其进行特征描述。