Henry Marine, Lavigne Rob, Debarbieux Laurent
Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Department of Microbiology, Paris, France.
Antimicrob Agents Chemother. 2013 Dec;57(12):5961-8. doi: 10.1128/AAC.01596-13. Epub 2013 Sep 16.
The potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis of in vitro observations, the parameters used to guide their choice among billions of available bacteriophages are still not clearly defined. We made use of a mouse lung infection model and a bioluminescent strain of Pseudomonas aeruginosa to compare the activities in vitro and in vivo of a set of nine different bacteriophages (PAK_P1, PAK_P2, PAK_P3, PAK_P4, PAK_P5, CHA_P1, LBL3, LUZ19, and PhiKZ). For seven bacteriophages, a good correlation was found between in vitro and in vivo activity. While the remaining two bacteriophages were active in vitro, they were not sufficiently active in vivo under similar conditions to rescue infected animals. Based on the bioluminescence recorded at 2 and 8 h postinfection, we also define for the first time a reliable index to predict treatment efficacy. Our results showed that the bacteriophages isolated directly on the targeted host were the most efficient in vivo, supporting a personalized approach favoring an optimal treatment.
利用各种动物模型现已充分证实噬菌体疗法治疗由抗生素耐药菌引起的感染的潜力。虽然基于体外观察，众多新分离出的噬菌体被宣称是潜在的治疗候选物，但在数十亿种可用噬菌体中指导选择它们的参数仍未明确界定。我们利用小鼠肺部感染模型和铜绿假单胞菌的发光菌株，比较了一组九种不同噬菌体（PAK_P1、PAK_P2、PAK_P3、PAK_P4、PAK_P5、CHA_P1、LBL3、LUZ19和PhiKZ）的体外和体内活性。对于七种噬菌体，在体外和体内活性之间发现了良好的相关性。虽然其余两种噬菌体在体外有活性，但在类似条件下在体内活性不足，无法挽救受感染的动物。基于感染后2小时和8小时记录的生物发光，我们还首次定义了一个可靠的指标来预测治疗效果。我们的结果表明，直接在目标宿主上分离的噬菌体在体内最有效，支持采用个性化方法以实现最佳治疗。
