Effects of empagliflozin and metformin on biofilm formation and pathogenicity factors of urinary Escherichia coli isolates.

Abstract

Escherichia coli, a major cause of urinary tract infections (UTIs), forms biofilms that contribute to antimicrobial resistance. Antidiabetic medications have gained attention for their potential antimicrobial effects, though data remain limited. This study investigated the inhibitory effects of empagliflozin and metformin against urinary E. coli isolates. Minimum inhibitory concentrations (MICs) were determined via broth microdilution, and synergistic interactions were assessed using the checkerboard method. Biofilm inhibition at sub-inhibitory drug concentrations was evaluated spectrophotometrically, and gene expression of fimH and luxS, were analyzed using RT-qPCR. Empagliflozin and metformin inhibited bacterial growth, with MICs ranging from 3.12-6.25 mg/mL and 25-50 mg/mL, respectively. A synergistic effect was observed in two isolates. Both drugs significantly reduced biofilm formation (51.8-72.9%) and downregulated fimH and luxS gene expression (p < 0.01). This study showed that empagliflozin and metformin could have inhibitory effects against urinary E. coli isolates, supporting their potential in drug repurposing strategies. Empagliflozin and metformin demonstrated significant dose-dependent in vitro antivirulence and antibiofilm activities, further supported by the downregulation of key virulence-associated genes (fimH and luxS). To the best of our knowledge, this is the first report investigating the in vitro effects of empagliflozin against urinary E. coli isolates, and further investigation is required to determine the impact of antidiabetic medications on E. coli.