Genética, Facultad de Ciencias, Universidad de Extremadura, Avda. de Elvas s/n, 06006, Badajoz, Spain.
Escuela Politécnica, Universidad de Extremadura, Avda. de la Universidad s/n, 10003, Cáceres, Spain.
Sci Rep. 2022 Feb 14;12(1):2458. doi: 10.1038/s41598-022-06422-1.
The application of bacteriophages as antibacterial agents has many benefits in the "post-antibiotic age". To increase the number of successfully targeted bacterial strains, phage cocktails, instead of a single phage, are commonly formulated. Nevertheless, there is currently no consensus pipeline for phage cocktail development. Thus, although large cocktails increase the spectrum of activity, they could produce side effects such as the mobilization of virulence or antibiotic resistance genes. On the other hand, coinfection (simultaneous infection of one host cell by several phages) might reduce the potential for bacteria to evolve phage resistance, but some antagonistic interactions amongst phages might be detrimental for the outcome of phage cocktail application. With this in mind, we introduce here a new method, which considers the host range and each individual phage-host interaction, to design the phage mixtures that best suppress the target bacteria while minimizing the number of phages to restrict manufacturing costs. Additionally, putative phage-phage interactions in cocktails and phage-bacteria networks are compared as the understanding of the complex interactions amongst bacteriophages could be critical in the development of realistic phage therapy models in the future.
噬菌体作为抗菌剂在“后抗生素时代”有许多好处。为了增加成功靶向细菌菌株的数量，通常会组合使用噬菌体鸡尾酒，而不是单一噬菌体。然而，目前还没有噬菌体鸡尾酒开发的共识流程。因此，尽管大型鸡尾酒可以增加活性谱，但它们可能会产生副作用，例如毒力或抗生素耐药性基因的转移。另一方面，共感染（即几个噬菌体同时感染一个宿主细胞）可能会降低细菌进化出噬菌体抗性的可能性，但噬菌体之间的一些拮抗相互作用可能会对噬菌体鸡尾酒应用的结果产生不利影响。考虑到这一点，我们在这里介绍了一种新方法，该方法考虑了宿主范围和每个噬菌体-宿主相互作用，以设计出最佳的噬菌体混合物，在最大限度地减少噬菌体数量以限制制造成本的同时，抑制目标细菌。此外，还比较了鸡尾酒和噬菌体-细菌网络中的假定噬菌体-噬菌体相互作用，因为了解噬菌体之间的复杂相互作用在未来开发现实的噬菌体治疗模型中可能至关重要。
