Evaluation of a novel Potentiator of Antibiotic (PA) effect on Proteus mirabilis-induced urinary tract infection (UTI) in mice

Abstract

Proteus mirabilis is able to induce clinical symptoms of the urogenital tract infection (UTI) and form crystalline biofilm made of a variety of bacteria that are highly resistant to conventional antimicrobial drugs. The presented work was designed to study the antibiotic potentiation effect of PA in mice with UTI. They were divided into 5 groups: intact, positive control, Amoxicillin group, PA group, amoxicillin and PA group. UTI was induced by inoculation of P. mirabilis (1.5×10⁹ CFU/mL), then animals received treatment for 14 days. Animals that received amoxicillin and PA displayed a normal rate of weight gain in comparison to the positive control (p < 0.01). The combined therapy also normalized in the levels of red blood cells, hematocrit, and hemoglobin, as well as white blood cells, lymphocytes, monocytes, and granulocytes (p < 0.01), indicating an alleviation of the inflammatory process. A significant rise of liver transaminases: ALT and AST, as well as in the levels of BUN and CREAT, was noted in the group of mice with UTI, no therapy (p < 0.01). However, the combined therapy of led to significant alleviation of all of these markers (p < 0.01), indicating normal function of the liver and kidneys. Finally, the histological examination revealed that the combined therapy had a nephroprotective effect, showing more intact structure, fewer degenerative processes and reduced congestion in contrast to the positive control. Thus, a novel drug PA, due to its ability to potentiate the efficacy of antimicrobial drugs, can offer a perspective approach for the treatment of infectious diseases.