Oliveira Hugo, Pinto Graça, Hendrix Hanne, Noben Jean-Paul, Gawor Jan, Kropinski Andrew M, Łobocka Małgorzata, Lavigne Rob, Azeredo Joana
Centre of Biological Engineering, Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Braga, Portugal.
Laboratory of Gene Technology, Katholieke Universiteit Leuven, Leuven, Belgium.
Appl Environ Microbiol. 2017 Nov 16;83(23). doi: 10.1128/AEM.01567-17. Print 2017 Dec 1.
is emerging as a new opportunistic pathogen with high antibiotic resistance. The need to find alternative methods to control antibiotic-resistant bacteria and the recent advances in phage therapy motivate the search for new phages able to infect spp. This study describes the isolation and characterization of an obligatory lytic phage, vB_PreS_PR1 (PR1), with therapeutic potential against drug-resistant PR1 is a siphovirus. Its virion DNA size (118,537 bp), transcriptional organization, terminal repeats (10,461 bp), and nicks in the 3'-to-5' strand are similar to those of phage T5. However, sequence similarities of PR1 to phages of the genus at the DNA and protein levels are limited, suggesting that it belongs to a new species within the family. PR1 exhibits the ability to kill antibiotic-resistant strains, is highly specific to the species, and did not present known genomic markers indicating a temperate lifestyle. The lack of homologies between its proteins and proteins of the only other sequenced prophage, Redjac, suggests that these two phages evolved separately and may target different host proteins. The alarming increase in the number of bacteria resistant to antibiotics has been observed worldwide. This is particularly true for Gram-negative bacteria. For certain of their strains, no effective antibiotics are available. sp. has been a neglected pathogen but is emerging as a multidrug-resistant bacterium. This has revived interest in bacteriophages as alternative therapeutic agents against this bacterium. We describe the morphological, physiological, and genomic characterization of a novel lytic virus, PR1, which is able to kill drug-resistant clinical isolates. Genomic and phylogenetic analyses indicate that PR1 is a distant relative of genus representatives. The lack of known virulence- or temperate lifestyle-associated genes in the genome of PR1 makes this phage a potential candidate for therapeutic use. Analysis of its genome also improves our knowledge of the ecology and diversity of T5-like siphoviruses, providing a new link for evolutionary studies of this phage group.
正作为一种具有高抗生素抗性的新型机会性病原菌出现。寻找控制抗生素抗性细菌的替代方法的需求以及噬菌体疗法的最新进展促使人们寻找能够感染 种的新噬菌体。本研究描述了一种具有治疗耐药性 潜力的 obligatory 裂解性噬菌体 vB_PreS_PR1（PR1）的分离和特性。PR1 是一种长尾噬菌体。其病毒体 DNA 大小（118,537 碱基对）、转录组织、末端重复序列（10,461 碱基对）以及 3' 到 5' 链上的切口与噬菌体 T5 相似。然而，PR1 与 属噬菌体在 DNA 和蛋白质水平上的序列相似性有限，这表明它属于 科内的一个新物种。PR1 表现出杀死抗生素抗性菌株的能力，对该物种具有高度特异性，并且没有呈现表明温和生活方式的已知基因组标记。其蛋白质与唯一另一个已测序的 原噬菌体 Redjac 的蛋白质之间缺乏同源性，这表明这两种噬菌体是独立进化的，并且可能靶向不同的宿主蛋白质。在全球范围内都观察到了对抗生素耐药细菌数量的惊人增长。革兰氏阴性菌尤其如此。对于它们的某些菌株，没有有效的抗生素可用。 种一直是被忽视的病原菌，但正作为一种多重耐药菌出现。这重新激发了人们对噬菌体作为对抗这种细菌的替代治疗剂的兴趣。我们描述了一种新型裂解病毒 PR1 的形态、生理和基因组特征，它能够杀死耐药性 临床分离株。基因组和系统发育分析表明 PR1 是 属代表的远亲。PR1 基因组中缺乏已知的与毒力或温和生活方式相关的基因，这使得该噬菌体成为治疗用途的潜在候选者。对其基因组的分析也增进了我们对 T5 样长尾噬菌体的生态学和多样性的了解，为该噬菌体群体的进化研究提供了新的联系。
