Bacteriophage P2-71: a promising therapeutic against multidrug-resistant Proteus mirabilis in urinary tract infections

作者：Ruihu Wu, Zhiyou Dong, Yunjiang Liu, Jialiang Xin, Yuxi Duan, Haohong Zheng, Yi‐Zhou Yang, Hualin Fu, Zhijun Zhong, Haifeng Liu, Ziyao Zhou, Yixin Huang, Guangneng Peng · 发表于：Frontiers in Veterinary Science · 年份：2024 · DOI：10.3389/fvets.2024.1445264 · 被引用次数：7 · 研究领域：Bacteriophages and microbial interactions、Microbial infections and disease research、Bacterial Identification and Susceptibility Testing

Background Proteus mirabilis 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 Proteus mirabilis in vivo and in vitro environments. Methods The in vitro therapeutic potential of bacteriophage P2-71 was assessed through the ability of phage to kill Proteus mirabilis by using a plate counting assay, and biofilm inhibition and biofilm lysis assays using a microtitre plate method. Additionally, an in vivo 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. Results In vitro , bacteriophage P2-71 achieved significant reductions in P. mirabilis concentrations, with log reductions of 1.537 and 0.7009 CFU/mL in laboratory and urine environments, respectively ( p < 0.001). The phage also decreased biofilm formation by 34–49% and lysed 15–25% of mature biofilms at various multiplicities of infection (MOIs) ( p < 0.001). In vivo , phage treatment significantly lowered bacterial concentrations in the urine on Days 1 and 3 ( p < 0.0001), achieving a maximum reduction of 4.602 log₁₀...