Abstract：
Antimicrobial resistance is an escalating threat with few new therapeutic options in the pipeline. Urinary tract infections (UTIs) are one of the most prevalent bacterial infections globally and are prone to becoming recurrent and antibiotic resistant. We discovered and characterized six novel Autographiviridae and Guernseyvirinae bacterial viruses (phage) against uropathogenic Escherichia coli (UPEC), a leading cause of UTIs. The phage genomes were between 39,471 bp - 45,233 bp, with 45.0%-51.0% GC%, and 57-84 predicted coding sequences per genome. We show that tail fiber domain structure, predicted host capsule type, and host antiphage repertoire correlate with phage host range. In vitro characterisation of phage cocktails showed synergistic improvement against a mixed UPEC strain population and when sequentially dosed. Together, these phage are a new set extending available treatments for UTI from UPEC, and phage vM_EcoM_SHAK9454 represents a promising candidate for further improvement through engineering.
摘要：
抗菌素耐药性是一个不断升级的威胁，几乎没有新的治疗选择。尿路感染(UTI)是全球最普遍的细菌感染之一,并且易于变得复发性和抗生素抗性。我们发现并鉴定了六种针对尿路致病性大肠杆菌（UPEC）的新型自拟病毒科和Guernseyvirinae细菌病毒（噬菌体），UTI的主要原因。噬菌体基因组在39,471bp-45,233bp之间，45.0%-51.0%GC%，和每个基因组57-84个预测编码序列。我们证明了尾部纤维结构域的结构，预测的宿主胶囊类型，和宿主抗噬菌体库与噬菌体宿主范围相关。噬菌体混合物的体外表征显示出针对混合UPEC菌株群体和顺序给药时的协同改善。一起,这些噬菌体是一套新的，从UPEC扩展了UTI的可用治疗方法，和噬菌体vM_EcoM_SHAK9454代表了通过工程进一步改进的有希望的候选者。
