Repurposing Metformin to Combat Multidrug-Resistant Proteus Mirabilis in Diabetic Foot Ulcers: Insights into Antibiotic Resistance and Some ABC Efflux Pump Genes

Abstract

Objective: To evaluate the antibiotic resistance profile, distribution of ABC efflux pump genes, and the in vitro antibacterial activity of metformin against Proteus mirabilis isolated from diabetic foot ulcers.

Study Design: Cross-sectional laboratory-based study
Place and Duration of Study: This study was conducted at the Department of Biology, College of Science for Women, University of Babylon, in collaboration with Al-Marjan Teaching Hospital and Al-Kafeel Specialized
Hospital, Iraq, from January 2026 to April 2026.

Methods: Clinical specimens from 188 patients with diabetic foot ulcers were cultured for bacterial isolation. Proteus mirabilis isolates were identified using standard microbiological methods. Antibiotic susceptibility testing was performed according to CLSI guidelines. The macA, macB, and tolC genes were detected by PCR, while the antibacterial activity and minimum inhibitory concentration (MIC) of metformin were determined using the broth microdilution method.

Results: Of 286 bacterial isolates recovered, 30 (10.49%) were identified as P. mirabilis. High multidrug resistance (MARI 0.38–0.84) was observed. The macA, macB, and tolC genes were detected in 90%, 86.7%, and 100% of
isolates, respectively. Metformin exhibited dose-dependent antibacterial activity with an MIC of 100 mg/mL.

Conclusion: MacAB-TolC efflux pumps are strongly associated with antimicrobial resistance in P. mirabilis isolated from diabetic foot ulcers. Metformin demonstrated promising adjunctive antibacterial activity and warrants further investigation as a potential therapeutic strategy.