NDM-1肺炎克雷伯菌裂解性噬菌体的分离鉴定及其对小鼠菌血症的治疗研究  

Using lytic bacteriophage to control murine bacteremia caused by NDM-1-producing Klebsiella pneumoniae strain BAA-2146

作　　者：路荣[1] 顾敬敏[1] 刘晓贺[1] 李跃[1] 韩东[1] 宋军[1] 冯新[1] 韩文瑜[1] 

机构地区：[1]吉林大学畜牧兽医学院,吉林长春130062

出　　处：《中国兽医学报》2012年第12期1747-1751,共5页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金资助项目(31130072)

摘　　要：噬菌体疗法在对抗多重耐药病原菌引起的感染方面具有很大的应用潜力。本研究从污水中分离到一株新的噬菌体，命名为NKP-1，并对噬菌体NKP-1的主要生物学特性进行研究。通过电镜观察确定NKP-1为短尾噬菌体，裂解试验表明该噬菌体为烈性噬菌体，具有很高的增值效率。体外试验表明它能够快速感染超强耐药的肺炎克雷伯菌株BAA-2146（NDM-1）并将其裂解。通过腹腔注射单一剂量的NKP-1（2×10^7pfu／mL）就可以有效地保护BAA-2146（4×10^9cfu／mL）感染引起的小鼠菌血症模型。在肺炎克雷伯菌BAA-2146与噬菌体NKP-1体外共同培养的过程中，我们分离到对该噬菌体具有抗性的突变菌株，通过动物试验确定该突变株表现为极低的毒力，且不影响NKP-1的治疗效果。本研究为利用噬菌体治疗多重耐药菌感染提供了理论基础与试验依据。Bacteriophage therapy could be an alternative to conventional antibiotic therapy against pathogens which are resistant to multiple antibiotics. In this study,a novel phage was isolated from sewage, termed NKP-1, which can replicate and lyse highly antibiotic resistant Klebsiella pneumoniae BAA-2146 （harboring the NDM-1 carbapenemase）. Basic characterization of NKP-1 demonstrated that the phage lysed BAA-2146 in vitro and in vivo. The phage resistance variant was found and isolated from BAA-2146 cultures when exposed to NKP-1,but the determination of MLD demonstrated an avirulent phage resistant variant. NKP-1 also displayed an ability in controlling BAA-2146 in a murine model of bacteremia. Bacteremic mice infected by lethal dose of BAA-2146 （4）〈 109 cfu/mL） were protected ef- fectively by intraperitoneal administration of a single dose of NKP-1 （2）〈 107 pfu/mL）. This novel phage have a great therapeutic potential as an antimicrobial agent target at antibiotic-resistant K. pneumoniae, and more importantly, this finding provides more forcible evidence towards the therapeutic use of phages to combat multi-drug resistant bacteria.

关 键 词：NDM-1 多重耐药性 肺炎克雷伯菌 噬菌体 

分 类 号：S852.659.1[农业科学—基础兽医学]