Molecular Virology and Microbiology Department, Baylor College of Medicine, Houston, TX 77030, USA.
Michael E. Debakey Veterans Affairs Medical Center, Houston, TX, 77030, USA.
Sci Rep. 2017 Apr 12;7:46151. doi: 10.1038/srep46151.
Multi-drug resistant (MDR) enteric bacteria are of increasing global concern. A clonal group, Escherichia coli sequence type (ST) 131, harbors both MDR and a deadly complement of virulence factors. Patients with an immunocompromised system are at high risk of infections with these E. coli and there is strong epidemiologic evidence that the human intestinal tract, as well as household pets, may be a reservoir. Here, we examine if phages are an effective treatment strategy against this clonal group in murine models of bacteremia that recapitulate clinical infections. Bacteriophages isolated from known E. coli reservoirs lyse a diverse array of MDR ST131 clinical isolates. Phage HP3 reduced E. coli levels and improved health scores for mice infected with two distinct ST131 strains. Efficacy was correlated to in vitro lysis ability by the infecting phage and the level of virulence of the E. coli strain. Importantly, it is also demonstrated that E. coli bacteremia initiated from translocation across the intestinal tract in an immunocompromised host is substantially reduced after phage treatment. This study demonstrates that phage, isolated from the environment and with little experimental manipulation, can be effective in combating even the most serious of infections by E. coli "superbugs".
多药耐药（MDR）肠道细菌引起了全球越来越多的关注。一个克隆群，大肠杆菌序列型（ST）131，同时具有 MDR 和致命的毒力因子。免疫系统受损的患者感染这些大肠杆菌的风险很高，有强有力的流行病学证据表明，人类肠道以及家庭宠物可能是其储存库。在这里，我们在模拟临床感染的菌血症小鼠模型中，研究了噬菌体是否是针对这种克隆群的有效治疗策略。从已知的大肠杆菌储存库中分离出的噬菌体可以裂解多种 MDR ST131 临床分离株。噬菌体 HP3 降低了感染两种不同 ST131 菌株的小鼠的大肠杆菌水平并提高了健康评分。疗效与感染噬菌体的体外裂解能力以及大肠杆菌菌株的毒力水平相关。重要的是，还证明了在免疫功能低下的宿主中，通过肠道易位引发的大肠杆菌菌血症在噬菌体治疗后显著减少。这项研究表明，从环境中分离出来的噬菌体，经过很少的实验操作，在对抗大肠杆菌“超级细菌”引起的最严重感染方面非常有效。
