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支持噬菌体 Kpn5 治疗由肺炎克雷伯菌引起的 BALB/c 小鼠烧伤感染的潜力的证据。

Evidence to support the therapeutic potential of bacteriophage Kpn5 in burn wound infection caused by Klebsiella pneumoniae in BALB/c mice.

机构信息

Basic Medical Sciences Building, Department of Microbiology, Panjab University, Chandigarh, India.

出版信息

J Microbiol Biotechnol. 2010 May;20(5):935-41. doi: 10.4014/jmb.0909.09010.

Abstract

The emergence of antibiotic-resistant bacterial strains is one of the most critical problems of modern medicine. Bacteriophages have been suggested as an alternative therapeutic agent for such bacterial infections. In the present study, we examined the therapeutic potential of phage Kpn5 in the treatment of Klebsiella pneumoniae B5055-induced burn wound infection in a mouse model. An experimental model of contact burn wound infection was established in mice employing K. pneumoniae B5055 to assess the efficacy of phage Kpn5 in vivo. Survival and stability of phage Kpn5 were evaluated in mice and the maximum phage count in various organs was obtained at 6 h and persisted until 36 h. The Kpn5 phage was found to be effective in the treatment of Klebsiella-induced burn wound infection in mice when phage was administered immediately after bacterial challange. Even when treatment was delayed up to 18 h post infection, when all animals were moribund, approximately 26.66% of the mice could be rescued by a single injection of this phage preparation. The ability of this phage to protect bacteremic mice was demonstrated to be due to the functional capabilities of the phage and not due to a nonspecific immune effect. The levels of pro-inflammatory cytokines (IL-1beta and TNF-alpha) and anti-inflammatory cytokines (IL-10) were significantly lower in sera and lungs of phage-treated mice than phage untreated control mice. The results of the present study bring out the potential of bacteriophage therapy as an alternate preventive approach to treat K. pneumoniae B5055- induced burn wound infections. This approach not only helps in the clearance of bacteria from the host but also protects against the ensuing inflammatory damage due to the exaggerated response seen in any infectious process.

摘要

抗生素耐药菌株的出现是现代医学面临的最严峻问题之一。噬菌体已被提议作为治疗此类细菌感染的替代治疗剂。在本研究中,我们研究了噬菌体 Kpn5 在治疗肺炎克雷伯菌 B5055 诱导的烧伤感染模型中的治疗潜力。使用肺炎克雷伯菌 B5055 在小鼠中建立接触性烧伤感染模型,评估噬菌体 Kpn5 在体内的疗效。评估了噬菌体 Kpn5 在小鼠中的生存能力和稳定性,并且在 6 小时和 36 小时时获得了各种器官中最大噬菌体数量。当噬菌体在细菌挑战后立即给药时,发现噬菌体 Kpn5 可有效治疗由肺炎克雷伯菌引起的烧伤感染。即使在感染后 18 小时才开始治疗,当所有动物都病危时,通过单次注射这种噬菌体制剂,约 26.66%的小鼠可以得到拯救。证明这种噬菌体保护菌血症小鼠的能力是由于噬菌体的功能能力,而不是由于非特异性免疫作用。与未用噬菌体处理的对照组小鼠相比,噬菌体处理小鼠的血清和肺中的促炎细胞因子(IL-1β和 TNF-α)和抗炎细胞因子(IL-10)水平明显降低。本研究的结果表明噬菌体治疗具有作为替代预防方法来治疗肺炎克雷伯菌 B5055 诱导的烧伤感染的潜力。这种方法不仅有助于从宿主清除细菌,而且还可以防止由于任何感染过程中所见的过度反应而引起的继发炎症损伤。

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