Repurposing Fingolimod as an Antibacterial and Antibiofilm Agent against Carbapenem-Resistant Acinetobacter baumannii.

The inappropriate use of antibiotics has contributed to the rise of multidrug-resistant bacteria. Among these, carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a critical global health challenge because of its extensive drug resistance. Accordingly, the World Health Organization has classified CRAB as a high-priority pathogen. To address this issue, this study evaluated the antibacterial and antibiofilm activities of fingolimod, a drug used to treat multiple sclerosis, against CRAB. The minimum inhibitory concentration was determined to assess the antibiotic susceptibility of clinical isolates and the antibacterial effect of fingolimod. Biofilm inhibition and eradication were evaluated using biofilm inhibitory concentration and biofilm eradication concentration assays, respectively. Metabolic activity within biofilms was analyzed using the XTT reduction assay and confocal laser scanning microscopy (CLSM), and the expression levels of carbapenemase- and biofilm-associated genes were measured by quantitative reverse transcription polymerase chain reaction. All A. baumannii isolates exhibited carbapenem resistance, and fingolimod inhibited bacterial growth by up to 98% at concentrations of 4-8 μg/mL. It suppressed biofilm formation in a concentration-dependent manner and effectively eradicated mature biofilms. Metabolic activity decreased progressively with increasing concentration, as consistently confirmed by both quantitative XTT analysis and CLSM imaging. Furthermore, fingolimod treatment downregulated all target genes. These findings indicate its strong therapeutic potential against CRAB by targeting both planktonic cells and biofilms.