摘要

抗生素疗效的恶化正在推动全球研究人员朝着诸如噬菌体疗法等替代技术：使用称为噬菌体的细菌病毒治愈感染性疾病。在以前的一篇论文中，我们分离了噬菌体EFDG1，它对抗最具有挑战性的致病物种万古霉素耐药肠球菌（VRE）的浮游生物和生物膜培养都非常有效。因此，它是用于噬菌体治疗的有前景的噬菌体。进一步的实验揭示了EFDG1噬菌体抗性突变体EFDG1r的出现。这种对抗生素的自发抗药性将是灾难性的，但是对于噬菌体疗法来说，这只是一个小小的障碍。我们迅速并成功地分离出一种新的噬菌体EFLK1，该抗体证明对抵抗突变体EFDG1r及其亲本VRE粪肠球菌V583有效。此外，将鸡尾酒中的两种噬菌体组合产生对粪肠球菌V583菌株的累加效应，而不管它们是抗生素还是噬菌体抗性谱。分析了两种噬菌体的基因组序列，基因，突变和tRNA含量的差异。这项工作是噬菌体治疗最显着优点之一的概念验证，即能够轻松克服新出现的耐药细菌

The deteriorating effectiveness of antibiotics is propelling researchers worldwide towards alternative techniques such as phage therapy: curing infectious diseases using viruses of bacteria called bacteriophages. In a previous paper, we isolated phage EFDG1, highly effective against both planktonic and biofilm cultures of one of the most challenging pathogenic species, the vancomycin-resistant Enterococcus (VRE). Thus, it is a promising phage to be used in phage therapy. Further experimentation revealed the emergence of a mutant resistant to EFDG1 phage: EFDG1r. This kind of spontaneous resistance to antibiotics would be disastrous occurrence, however for phage-therapy it is only a minor hindrance. We quickly and successfully isolated a new phage, EFLK1, which proved effective against both the resistant mutant EFDG1r and its parental VRE, Enterococcus faecalis V583. Furthermore, combining both phages in a cocktail produced an additive effect against E. faecalis V583 strains regardless of their antibiotic or phage-resistance profile. An analysis of the differences in genome sequence, genes, mutations, and tRNA content of both phages is presented. This work is a proof-of-concept of one of the most significant advantages of phage therapy, namely the ability to easily overcome emerging resistant bacteria.

https://www.ncbi.nlm.nih.gov/pubmed/29541067