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Defeating Antibiotic- and Phage-Resistant Enterococcus faecalis Using a Phage Cocktail in Vitro and in a Clot Model

机译:在体外和凝块模型中使用噬菌体鸡尾酒击败抗生素和噬菌体肠球菌粪便

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摘要

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.
机译:抗生素的劣化效果是推动全世界的研究人员,以诸如噬菌体疗法等替代技术:使用叫做噬菌体的细菌病毒治愈传染病。在先前的论文中,我们分离噬菌体EFDG1,对氏菌和生物膜培养的高度有效,具有最具挑战性的致病性物种之一,耐风坎霉素的肠球菌(VRE)。因此,它是在噬菌体疗法中使用的承诺噬菌体。进一步的实验表明,对EFDG1噬菌体的抗突变体的出现:EFDG1R。这种自发抗生素的抗性将是灾难性的发生,但对于噬菌体治疗而言,这只是一种轻微的障碍。我们迅速且成功地孤立了新噬菌体,EFLK1,其证明对抗抗性突变体EFDG1R及其父母VRE,肠球菌粪便v583。此外,无论其抗生素或噬菌体抗性分布如何,将两种噬菌体组合在鸡尾酒中产生了对E. FAECALIS V583菌株的添加剂效应。介绍了两种噬菌体的基因组序列,基因,突变和TRNA含量的差异。这项工作是噬菌体疗法最显着的优势之一的概念概念,即容易克服出现抗性细菌的能力。

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