A Novel Therapeutic Approach: Phage and Alhagi maurorum Synergy Against Kidney and Bladder Infection Caused by Proteus mirabilis in BALB/c Mice

Abstract

Catheter-associated urinary tract infections (CAUTIs) caused by Proteus mirabilis biofilms present significant challenges due to escalating multidrug resistance, highlighting the urgent need for alternative therapeutic strategies. This study evaluates a novel combinatorial approach employing a cocktail of two lytic bacteriophages (Isf-Pm1 and Isf-Pm2) in conjunction with Alhagi maurorum ethanolic extract (AME) to reduce bacterial burden in an established murine model of catheter-associated infection. We hypothesized that the synergistic activity of phages and AME would enhance treatment efficacy, impede resistance development, and promote infection clearance. Using a catheterized BALB/c mouse model with five experimental groups (n = 6 per group), we assessed the therapeutic efficacy of the phage-AME combination across varying dosages and treatment durations. Bacterial load (CFU/mL) was quantified from homogenized kidney and bladder tissues following treatment. The combination of phages at a multiplicity of infection (MOI) of 1 and AME at 750 mg/kg administered over 7 days produced the most pronounced antibacterial effect, achieving a 7-log(10) reduction in renal bacterial counts and a 5.3-log(10) reduction in bladder bacterial counts. Notably, extending the treatment duration from 3 to 7 days significantly enhanced bacterial clearance in renal tissues (p < 0.0001), highlighting the critical importance of prolonged therapy for optimizing outcomes. Our findings demonstrate that both dosage and treatment duration significantly influence the therapeutic efficacy of the phage-AME combination, emphasizing the necessity of protocol optimization to improve clinical outcomes for patients with kidney and bladder infections. Collectively, this study presents a promising, mechanistically grounded alternative strategy for combating biofilm-associated CAUTIs and warrants further translational investigation.