Bacteriophages from ExPEC Reservoirs Kill Pandemic Multidrug-Resistant Strains of Clonal Group ST131 in Animal Models of Bacteremia.
Bacteriophages from ExPEC Reservoirs Kill Pandemic Multidrug-Resistant Strains of Clonal Group ST131 in Animal Models of Bacteremia.
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DOI：
10.1038/srep46151
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发表时间：
2017-04-12
影响因子：
4.6
通讯作者：
Maresso AW
中科院分区：
文献类型：
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作者：
Green SI;Kaelber JT;Ma L;Trautner BW;Ramig RF;Maresso AW
多药耐药(MDR)肠道细菌日益受到全球关注。克隆组，大肠杆菌序列型(ST)131，同时含有MDR和致命的毒力因子补充。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，人类肠道以及家养宠物可能是宿主。在这里，我们检查噬菌体是否是针对这个克隆组的有效治疗策略，在总结临床感染的菌血症小鼠模型中。从已知的大肠杆菌储存库中分离出的噬菌体可裂解一系列不同的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。药效与感染噬菌体的体外裂解能力和菌株的毒力水平有关。重要的是，研究还表明，在免疫功能低下的宿主体内，由肠道移位引起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，几乎不需要实验操作，即使是最严重的大肠杆菌“超级细菌”感染也可以有效地对抗。
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”.