Cao Fang, Wang Xitao, Wang Linhui, Li Zhen, Che Jian, Wang Lili, Li Xiaoyu, Cao Zhenhui, Zhang Jiancheng, Jin Liji, Xu Yongping
School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China ; Orthopedics Research Center, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China.
School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.
Biomed Res Int. 2015;2015:752930. doi: 10.1155/2015/752930. Epub 2015 Mar 23.
Multidrug-resistant Klebsiella pneumoniae (MRKP) has steadily grown beyond antibiotic control. However, a bacteriophage is considered to be a potential antibiotic alternative for treating bacterial infections. In this study, a lytic bacteriophage, phage 1513, was isolated using a clinical MRKP isolate KP 1513 as the host and was characterized. It produced a clear plaque with a halo and was classified as Siphoviridae. It had a short latent period of 30 min, a burst size of 264 and could inhibit KP 1513 growth in vitro with a dose-dependent pattern. Intranasal administration of a single dose of 2×10(9) PFU/mouse 2 h after KP 1513 inoculation was able to protect mice against lethal pneumonia. In a sublethal pneumonia model, phage-treated mice exhibited a lower level of K. pneumoniae burden in the lungs as compared to the untreated control. These mice lost less body weight and exhibited lower levels of inflammatory cytokines in their lungs. Lung lesion conditions were obviously improved by phage therapy. Therefore, phage 1513 has a great effect in vitro and in vivo, which has potential to be used as an alternative to an antibiotic treatment of pneumonia that is caused by the multidrug-resistant K. pneumoniae.
多重耐药肺炎克雷伯菌(MRKP)已逐渐发展到超出抗生素控制范围。然而,噬菌体被认为是治疗细菌感染的一种潜在抗生素替代品。在本研究中,以临床分离的MRKP菌株KP 1513为宿主分离出一种裂解性噬菌体,即噬菌体1513,并对其进行了特性分析。它产生了带有晕圈的清晰噬菌斑,被归类为长尾噬菌体科。其潜伏期短,为30分钟,裂解量为264,并且能够在体外以剂量依赖模式抑制KP 1513的生长。在接种KP 1513后2小时,以2×10⁹ PFU/小鼠的单剂量进行鼻内给药能够保护小鼠免受致死性肺炎的侵害。在亚致死性肺炎模型中,与未治疗的对照组相比,经噬菌体治疗的小鼠肺部肺炎克雷伯菌载量较低。这些小鼠体重减轻较少,肺部炎症细胞因子水平较低。噬菌体疗法明显改善了肺部病变情况。因此,噬菌体1513在体外和体内均有显著效果,有潜力作为治疗由多重耐药肺炎克雷伯菌引起的肺炎的抗生素替代品。