Bacteriophage P2-71: a promising therapeutic against multidrug-resistantin urinary tract infections.

Abstract

BACKGROUND: 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 againstandenvironments. METHODS: Thetherapeutic potential of bacteriophage P2-71 was assessed through the ability of phage to killby using a plate counting assay, and biofilm inhibition and biofilm lysis assays using a microtitre plate method. Additionally, anUTI model in C57BL/6Jmice was developed via urethral inoculation of the bacterium. Phage therapy was administered through urethral injection over a period of 5&#x2009;days. Therapeutic outcomes were measured by analyzing bacterial load, phage titer, inflammatory markers, and histopathological changes in the urine, urogenital tissues, and spleen. RESULTS: , bacteriophage P2-71 achieved significant reductions inconcentrations, with log reductions of 1.537 and 0.7009&#x2009;CFU/mL in laboratory and urine environments, respectively (&#x2009;<&#x2009;0.001). The phage also decreased biofilm formation by 34-49% and lysed 15-25% of mature biofilms at various multiplicities of infection (MOIs) (&#x2009;<&#x2009;0.001)., phage treatment significantly lowered bacterial concentrations in the urine on Days 1 and 3 (&#x2009;<&#x2009;0.0001), achieving a maximum reduction of 4.602 log&#x2081;&#x2080; CFU/mL; however, its effectiveness diminished by Day 5 (&#x2009;>&#x2009;0.05). Concurrently, phage titers decreased over time. Importantly, phage treatment notably reduced bacterial load in the bladder, kidneys, and spleen (&#x2009;<&#x2009;0.001). Inflammatory markers such as IL-6, IL-1&#x3b2;, and TNF-were significantly lower in the treatment group, especially in the bladder (&#x2009;<&#x2009;0.0001), indicating an effective reduction in inflammation. Histopathological analysis showed significant mitigation of tissue damage. CONCLUSION: 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.