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YH6噬菌体在小鼠出血性肺炎模型中的治疗效果。

Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model.

作者信息

Yang Mei, Du Chongtao, Gong Pengjuan, Xia Feifei, Sun Changjiang, Feng Xin, Lei Liancheng, Song Jun, Zhang Lei, Wang Bin, Xiao Feng, Yan Xinwu, Cui Ziyin, Li Xinwei, Gu Jingmin, Han Wenyu

机构信息

College of Veterinary Medicine, Jilin University, Changchun 130062, PR China.

College of Animal Science, Jilin University, Changchun 130062, PR China.

出版信息

Res Microbiol. 2015 Oct;166(8):633-43. doi: 10.1016/j.resmic.2015.07.008. Epub 2015 Aug 6.

Abstract

The treatment, in farmed mink, of hemorrhagic pneumonia caused by multidrug-resistant Pseudomonas aeruginosa strains has become increasingly difficult. This study investigated the potential use of phages as a therapy against hemorrhagic pneumonia caused by P. aeruginosa in a murine hemorrhagic pneumonia model. An N4-like phage designated YH6 was isolated using P. aeruginosa strain D9. YH6 is a virulent phage with efficient and broad host lytic activity against P. aeruginosa. No bacterial virulence- or lysogenesis-related ORF is present in the YH6 genome, making it eligible for use in phage therapy. In our murine experiments, a single intranasal administration of YH6 (2 × 10(7) PFU) 2 h after D9 intranasal injections at double minimum lethal dose was sufficient to protect mice against hemorrhagic pneumonia. The bacterial load in the lungs of YH6-protected mice was less than 10(3) CFU/g within 24 h after challenge and ultimately became undetectable, whereas the amount of bacteria in the lung tissue derived from unprotected mice was more than 10(8) CFU/g within 24 h after challenge. In view of its protective efficacy in this murine hemorrhagic pneumonia model, YH6 may serve as an alternative treatment strategy for infections caused by multidrug-resistant P. aeruginosa.

摘要

治疗由多重耐药铜绿假单胞菌菌株引起的养殖水貂出血性肺炎变得越来越困难。本研究在小鼠出血性肺炎模型中调查了噬菌体作为治疗铜绿假单胞菌引起的出血性肺炎的潜在用途。使用铜绿假单胞菌菌株D9分离出一种名为YH6的N4样噬菌体。YH6是一种烈性噬菌体,对铜绿假单胞菌具有高效且广泛的宿主裂解活性。YH6基因组中不存在与细菌毒力或溶原性相关的开放阅读框,使其有资格用于噬菌体治疗。在我们的小鼠实验中,在以两倍最小致死剂量经鼻注射D9后2小时,单次经鼻给予YH6(2×10⁷噬斑形成单位)足以保护小鼠免受出血性肺炎的侵害。在攻毒后24小时内,YH6保护的小鼠肺部细菌载量低于10³CFU/g,最终变得无法检测到,而未受保护的小鼠肺组织中的细菌数量在攻毒后24小时内超过10⁸CFU/g。鉴于其在该小鼠出血性肺炎模型中的保护效果,YH6可能作为多重耐药铜绿假单胞菌引起的感染的替代治疗策略。

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