Empagliflozin modulates biofilm formation and virulence-associated gene expression in multidrug-resistant...

Multidrug-resistant (MDR) pathogens represent a major global health threat, necessitating the development of alternative therapeutic strategies. Drug repurposing has emerged as a promising approach to identify non-antibiotic agents with antimicrobial and antivirulence potential. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, widely used as antidiabetic agents, have recently attracted attention due to their potential antimicrobial properties. However, evidence regarding the antimicrobial activity of SGLT-2 inhibitors, particularly empagliflozin (EMP), remains limited. This study aimed to evaluate the in vitro antimicrobial and antibiofilm effects of EMP against clinical methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii isolates. Minimum inhibitory concentrations (MICs) of empagliflozin were determined using the broth microdilution method. The antibiofilm activity of EMP was assessed spectrophotometrically, while its effect on bacterial cell viability was evaluated using a fluorometric resazurin assay. Additionally, changes in the expression of biofilm-related genes (icaA, icaD, bap, and adeG) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Empagliflozin demonstrated antimicrobial activity against tested clinical isolates MRSA (n = 3) and A. baumannii isolates (n = 3), with MIC values ranging from 3125 to 6250 µg/mL. EMP significantly inhibited biofilm formation in MRSA and A. baumannii strains by 79% and 85%, respectively. Gene expression analysis revealed downregulation of icaA and icaD in MRSA isolates, while bap and adeG expression levels were reduced by 85% and 64%, respectively, in A. baumannii strains. These preliminary and in vitro findings showed that empagliflozin could be a potential candidate for combating MDR pathogens. Further studies will be required to clarify its antimicrobial potential and underlying mechanisms of action.