Isolation and evaluation of bacteriophage cocktail for the control of colistin-resistant Escherichia coli

IF 3.3 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis Pub Date : 2024-10-21 DOI:10.1016/j.micpath.2024.107056

Xiaolin Zhu , Tianshi Xiao , Xuchen Jia , Xuan Ni , Xiaosong Zhang , Yizhuo Fang , Zhihui Hao

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引用次数: 0

Abstract

The frequent emergence of colistin-resistant E. coli worldwide drives the exploration of alternative therapies, and bacteriophages (phages) have emerged as promising candidates to tackle this challenge. In this study, three E. coli phages were isolated, screened, and evaluated against 96 colistin-resistant strains obtained from diverse sources. The combined recognition rate for these strains was 43.6 %, while individually it ranged from 17.0 % to 24.5 %. Notably, among the tested phages (FJ3-79, SD1-92L, and FJ4-63), FJ4-63 demonstrated exceptional characteristics in regulating host population dynamics upon infection by exhibiting a shorter latent period (20 min) and a larger burst size (95.99 ± 3.61 PFU/cell). Furthermore, it exhibited relative stability at pH 3–11 and below 60 °C. Transmission electron microscopy and genomic analysis classified phage FJ4-63 belongs to the Dhakavirus genus within the Straboviridae family. Its genome comprised a linear double-stranded DNA measuring 169,669 bp (containing 272 coding sequences) with a GC content of 39.76 %, of which 93 (34.2 %) had known functions, and the remaining 177 were annotated as hypothetical proteins. Additionally, two tRNAs were recognized, possess the “holin-endolysin” lytic system, and no resistance or virulence genes were detected. The phylogenetic tree and average nucleotide identity (ANI) analysis revealed that phage FJ4-63 exhibited the highest similarity to Escherichia phage C6 (679410.1), indicating a consistent close relationship within the same branch. The cocktail comprising three phages exhibits enhanced in vitro bactericidal efficacy compared to a single phage. At high doses with MOI = 100, it rapidly and completely eradicates bacteria within 1 h while significantly reducing bacterial biofilms. All this evidence suggests that lytic phages offer an effective solution for clinical treatment, with a phage cocktail demonstrating greater potential in the alternative management of colistin-resistant E. coli infections.

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用于控制耐大肠菌素大肠埃希氏菌的噬菌体鸡尾酒的分离和评估。

全球频繁出现耐大肠菌素的大肠杆菌，促使人们探索替代疗法，而噬菌体（噬菌体）已成为应对这一挑战的有希望的候选疗法。本研究分离、筛选了三种大肠杆菌噬菌体，并针对从不同来源获得的 96 株耐药菌株进行了评估。这些菌株的综合识别率为 43.6%，而单独识别率则从 17.0% 到 24.5% 不等。值得注意的是，在测试的噬菌体（FJ3-79、SD1-92L 和 FJ4-63）中，FJ4-63 在感染后调节宿主种群动态方面表现出独特的特性，潜伏期较短（20 分钟），迸发量较大（95.99 ± 3.61 PFU/细胞）。此外，它在 pH 值为 3-11 和低于 60°C 时表现出相对稳定性。透射电子显微镜和基因组分析表明，噬菌体 FJ4-63 属于细小病毒科达卡病毒属。其基因组由线性双链 DNA 组成，长度为 169,669 bp（包含 272 个编码序列），GC 含量为 39.76%，其中 93 个序列（34.2%）具有已知功能，其余 177 个序列被注释为假定蛋白。此外，还识别出两个 tRNA，拥有 "holin-endolysin "溶菌系统，没有检测到抗性基因或毒力基因。系统发生树和平均核苷酸同一性（ANI）分析表明，噬菌体 FJ4-63 与埃希氏菌噬菌体 C6 的相似度最高（679410.1），表明在同一分支中存在一致的密切关系。与单一噬菌体相比，由三种噬菌体组成的鸡尾酒具有更强的体外杀菌效果。在 MOI = 100 的高剂量下，它能在 1 小时内迅速完全消灭细菌，同时显著减少细菌生物膜。所有这些证据表明，溶菌噬菌体为临床治疗提供了一种有效的解决方案，噬菌体鸡尾酒在替代性治疗耐秋水仙碱大肠杆菌感染方面具有更大的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microbial pathogenesis 医学-免疫学

CiteScore

7.40

自引率

2.60%

发文量

472

审稿时长

56 days

期刊介绍： Microbial Pathogenesis publishes original contributions and reviews about the molecular and cellular mechanisms of infectious diseases. It covers microbiology, host-pathogen interaction and immunology related to infectious agents, including bacteria, fungi, viruses and protozoa. It also accepts papers in the field of clinical microbiology, with the exception of case reports. Research Areas Include: -Pathogenesis -Virulence factors -Host susceptibility or resistance -Immune mechanisms -Identification, cloning and sequencing of relevant genes -Genetic studies -Viruses, prokaryotic organisms and protozoa -Microbiota -Systems biology related to infectious diseases -Targets for vaccine design (pre-clinical studies)