Kelly Abigail, Went Sam C, Mariano Giuseppina, Shaw Liam P, Picton David M, Duffner Samuel J, Coates Isabel, Herdman-Grant Ryan, Gordeeva Julia, Drobiazko Alena, Isaev Artem, Lee Yan-Jiun, Luyten Yvette, Morgan Richard D, Weigele Peter, Severinov Konstantin, Wenner Nicolas, Hinton Jay C D, Blower Tim R
Department of Biosciences, Durham University , Durham, UK.
Microbes in Health and Disease Theme, Newcastle University Biosciences Institute, Newcastle University , Newcastle upon Tyne, UK.
Appl Environ Microbiol. 2023 Sep 28;89(9):e0062323. doi: 10.1128/aem.00623-23. Epub 2023 Sep 5.
Bacteriophages (phages) outnumber bacteria ten-to-one and cause infections at a rate of 10 per second. The ability of phages to reduce bacterial populations makes them attractive alternative antibacterials for use in combating the rise in antimicrobial resistance. This effort may be hindered due to bacterial defenses such as Bacteriophage Exclusion (BREX) that have arisen from the constant evolutionary battle between bacteria and phages. For phages to be widely accepted as therapeutics in Western medicine, more must be understood about bacteria-phage interactions and the outcomes of bacterial phage defense. Here, we present the annotated genomes of 12 novel bacteriophage species isolated from water sources in Durham, UK, during undergraduate practical classes. The collection includes diverse species from across known phylogenetic groups. Comparative analyses of two novel phages from the collection suggest they may be founding members of a new genus. Using this Durham phage collection, we determined that particular BREX defense systems were likely to confer a varied degree of resistance against an invading phage. We concluded that the number of BREX target motifs encoded in the phage genome was not proportional to the degree of susceptibility. IMPORTANCE Bacteriophages have long been the source of tools for biotechnology that are in everyday use in molecular biology research laboratories worldwide. Phages make attractive new targets for the development of novel antimicrobials. While the number of phage genome depositions has increased in recent years, the expected bacteriophage diversity remains underrepresented. Here we demonstrate how undergraduates can contribute to the identification of novel phages and that a single City in England can provide ample phage diversity and the opportunity to find novel technologies. Moreover, we demonstrate that the interactions and intricacies of the interplay between bacterial phage defense systems such as Bacteriophage Exclusion (BREX) and phages are more complex than originally thought. Further work will be required in the field before the dynamic interactions between phages and bacterial defense systems are fully understood and integrated with novel phage therapies.
噬菌体的数量比细菌多九倍，且每秒以10次的速率引发感染。噬菌体减少细菌数量的能力使其成为对抗抗菌药物耐药性上升的有吸引力的替代抗菌剂。由于细菌防御机制（如噬菌体排除系统，BREX）的存在，这一努力可能会受到阻碍，这些防御机制源于细菌与噬菌体之间持续的进化斗争。为了使噬菌体在西方医学中被广泛接受为治疗剂，必须更多地了解细菌与噬菌体的相互作用以及细菌噬菌体防御的结果。在此，我们展示了在本科实践课程期间从英国达勒姆的水源中分离出的12种新型噬菌体物种的注释基因组。该集合包括来自已知系统发育组的不同物种。对该集合中的两种新型噬菌体的比较分析表明，它们可能是一个新属的创始成员。利用这个达勒姆噬菌体集合，我们确定特定的BREX防御系统可能赋予对入侵噬菌体不同程度的抗性。我们得出结论，噬菌体基因组中编码的BREX靶基序数量与易感性程度不成正比。重要性噬菌体长期以来一直是生物技术工具的来源，在全球分子生物学研究实验室中每天都在使用。噬菌体是开发新型抗菌剂的有吸引力的新靶点。虽然近年来噬菌体基因组沉积的数量有所增加，但预期的噬菌体多样性仍然代表性不足。在这里，我们展示了本科生如何为鉴定新型噬菌体做出贡献，以及英格兰的一个城市如何能够提供丰富的噬菌体多样性和发现新技术的机会。此外，我们证明了细菌噬菌体防御系统（如噬菌体排除系统，BREX）与噬菌体之间相互作用的复杂性比最初想象的更为复杂。在充分理解噬菌体与细菌防御系统之间的动态相互作用并将其与新型噬菌体疗法整合之前，该领域还需要进一步的研究。
