Wu Ruihu, Dong Zhiyou, Liu Yunjiang, Xin Jialiang, Duan Yuxi, Zheng Haohong, Yang Yizhou, Fu Hualin, Zhong Zhijun, Liu Haifeng, Zhou Ziyao, Huang Yixin, Peng Guangneng
Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Front Vet Sci. 2024 Sep 17;11:1445264. doi: 10.3389/fvets.2024.1445264. eCollection 2024.
is a Gram-negative, rod-shaped bacterium widely found in natural environments. It is known for causing a range of severe illnesses in mammals, particularly urinary tract infections (UTIs). This study evaluates the therapeutic efficacy of phage P2-71 against and environments.
The therapeutic potential of bacteriophage P2-71 was assessed through the ability of phage to kill by using a plate counting assay, and biofilm inhibition and biofilm lysis assays using a microtitre plate method. Additionally, an UTI model in C57BL/6Jmice was developed via urethral inoculation of the bacterium. Phage therapy was administered through urethral injection over a period of 5 days. Therapeutic outcomes were measured by analyzing bacterial load, phage titer, inflammatory markers, and histopathological changes in the urine, urogenital tissues, and spleen.
, bacteriophage P2-71 achieved significant reductions in concentrations, with log reductions of 1.537 and 0.7009 CFU/mL in laboratory and urine environments, respectively ( < 0.001). The phage also decreased biofilm formation by 34-49% and lysed 15-25% of mature biofilms at various multiplicities of infection (MOIs) ( < 0.001). , phage treatment significantly lowered bacterial concentrations in the urine on Days 1 and 3 ( < 0.0001), achieving a maximum reduction of 4.602 log₁₀ CFU/mL; however, its effectiveness diminished by Day 5 ( > 0.05). Concurrently, phage titers decreased over time. Importantly, phage treatment notably reduced bacterial load in the bladder, kidneys, and spleen ( < 0.001). Inflammatory markers such as IL-6, IL-1β, and TNF- were significantly lower in the treatment group, especially in the bladder ( < 0.0001), indicating an effective reduction in inflammation. Histopathological analysis showed significant mitigation of tissue damage.
The results demonstrated that bacteriophage P2-71 is a promising alternative therapy for UTIs caused by MDR . This bacteriophage therapy offers a viable strategy for managing infections where traditional antimicrobials fail, highlighting its potential in clinical applications.
[细菌名称]是一种革兰氏阴性杆菌，广泛存在于自然环境中。它以在哺乳动物中引发一系列严重疾病而闻名，尤其是尿路感染（UTIs）。本研究评估了噬菌体P2 - 71对[细菌名称]的治疗效果以及在不同环境中的作用。
通过噬菌斑计数法评估噬菌体P2 - 71杀死[细菌名称]的能力，以及使用微量滴定板法进行生物膜抑制和生物膜裂解试验，以此来评估噬菌体的治疗潜力。此外，通过尿道接种该细菌建立了C57BL/6J小鼠的UTI模型。通过尿道注射进行为期5天的噬菌体治疗。通过分析尿液、泌尿生殖组织和脾脏中的细菌载量、噬菌体滴度、炎症标志物和组织病理学变化来衡量治疗效果。
在实验室环境和尿液环境中，噬菌体P2 - 71使[细菌名称]浓度显著降低，分别降低了1.537 log和0.7009 CFU/mL（P < 0.001）。在不同感染复数（MOIs）下，该噬菌体还使生物膜形成减少了34 - 49%，并裂解了15 - 25%的成熟生物膜（P < 0.001）。在UTI小鼠模型中，噬菌体治疗在第1天和第3天显著降低了尿液中的细菌浓度（P < 0.0001），最大降低了4.602 log₁₀ CFU/mL；然而，到第5天其效果减弱（P > 0.05）。同时，噬菌体滴度随时间下降。重要的是，噬菌体治疗显著降低了膀胱、肾脏和脾脏中的细菌载量（P < 0.001）。治疗组中白细胞介素 - 6、白细胞介素 - 1β和肿瘤坏死因子等炎症标志物显著降低，尤其是在膀胱中（P < 0.0001），表明炎症得到有效减轻。组织病理学分析显示组织损伤明显减轻。
结果表明，噬菌体P2 - 71是治疗由多重耐药[细菌名称]引起的UTIs的一种有前景的替代疗法。这种噬菌体疗法为传统抗菌药物失效时的感染管理提供了一种可行策略，凸显了其在临床应用中的潜力。
