INTEGRATED TRANSCRIPTOMIC PROFILING OF THE Candida albicans RESPONSE TO THE SYNERGISTIC INTERACTION BETWEEN ATOMOXETINE AND FLUCONAZOLE

Candida species are notorious opportunistic pathogens that can cause severe infections, especially in immunocompromised and medically vulnerable patients. Despite the availability of various antifungal drugs, their efficacy is often limited by drug toxicity and antifungal resistance. Therefore, repurposing existing clinically approved drugs is a promising approach to addressing this challenge. In this study, we investigated the potential synergistic effects of combining the antidepressant atomoxetine (ATMX) with the antifungal agent fluconazole (FLC) against Candida albicans. Our results demonstrated that ATMX (31.25 μg/mL) and FLC (1.95 μg/mL) exhibited a trend toward synergistic activity C. albicans. We performed RNA-Seq analysis to investigate the transcriptional response of C. albicans treated with ATMX-FLC combination. Our analysis indicated that the combination has a significant impact on ribosome biogenesis, secondary metabolite biosynthesis, and metabolic pathways. Overall, our findings highlight the potential of repurposing clinically approved drugs as a novel therapeutic strategy for the treatment of Candida infections, which continue to pose a significant global public health challenge.