Cazares Adrián, García-Contreras Rodolfo, Pérez-Velázquez Judith
EMBL's European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, United Kingdom.
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom.
Front Microbiol. 2020 Nov 12;11:590294. doi: 10.3389/fmicb.2020.590294. eCollection 2020.
If there is something we have learned from the antibiotic era, it is that indiscriminate use of a therapeutic agent without a clear understanding of its long-term evolutionary impact can have enormous health repercussions. This knowledge is particularly relevant when the therapeutic agents are remarkably adaptable and diverse biological entities capable of a plethora of interactions, most of which remain largely unexplored. Although phage therapy (PT) undoubtedly holds the potential to save lives, its current efficacy in case studies recalls the golden era of antibiotics, when these compounds were highly effective and the possibility of them becoming ineffective seemed remote. Safe PT schemes depend on our understanding of how phages interact with, and evolve in, highly complex environments. Here, we summarize and review emerging evidence in a commonly overlooked theme in PT: bacteria-phage interactions. In particular, we discuss the influence of quorum sensing (QS) on phage susceptibility, the consequent role of phages in modulating bacterial cooperation, and the potential implications of this relationship in PT, including how we can use this knowledge to inform PT strategies. We highlight that the influence of QS on phage susceptibility seems to be widespread but can have contrasting outcomes depending on the bacterial host, underscoring the need to thoroughly characterize this link in various bacterial models. Furthermore, we encourage researchers to exploit competition experiments, experimental evolution, and mathematical modeling to explore this relationship further in relevant infection models. Finally, we emphasize that long-term PT success requires research on phage ecology and evolution to inform the design of optimal therapeutic schemes.
如果说我们从抗生素时代学到了什么，那就是在没有清楚了解一种治疗剂的长期进化影响的情况下不加区分地使用它，可能会对健康产生巨大影响。当治疗剂是具有极强适应性且能进行大量相互作用的多样生物实体（其中大多数在很大程度上仍未被探索）时，这一认识尤为重要。尽管噬菌体疗法（PT）无疑有拯救生命的潜力，但其在案例研究中的当前疗效让人回想起抗生素的黄金时代，那时这些化合物非常有效，而且它们失效的可能性似乎很遥远。安全的噬菌体疗法方案取决于我们对噬菌体如何在高度复杂的环境中相互作用和进化的理解。在这里，我们总结并回顾了噬菌体疗法中一个常被忽视的主题的新证据：细菌 - 噬菌体相互作用。特别是，我们讨论群体感应（QS）对噬菌体敏感性的影响、噬菌体在调节细菌合作中的相应作用，以及这种关系在噬菌体疗法中的潜在意义，包括我们如何利用这些知识为噬菌体疗法策略提供信息。我们强调群体感应对噬菌体敏感性的影响似乎很普遍，但根据细菌宿主的不同可能会有不同的结果，这突出了在各种细菌模型中彻底表征这种联系的必要性。此外，我们鼓励研究人员利用竞争实验、实验进化和数学建模在相关感染模型中进一步探索这种关系。最后，我们强调噬菌体疗法的长期成功需要对噬菌体生态学和进化进行研究，以为最佳治疗方案的设计提供信息。
