Exploring the anti-biofilm and gene regulatory effects of anti-inflammatory drugs on Candida albicans

Researchers have repurposed several existing anti-inflammatory drugs as potential antifungal agents in recent years. So, this study aimed to investigate the effects of anti-inflammatory drugs on the growth, biofilm formation, and expression of genes related to morphogenesis and pathogenesis in Candida albicans. The minimum inhibitory concentration (MIC) of anti-inflammatory drugs was assessed using the broth microdilution method. Biofilm formation in C. albicans was evaluated using XTT reduction assay following exposure to different concentrations of drugs. Additionally, the expression of adhesin-related genes (ALS1, ALS3), hyphal cell wall specific genes (EAP1, HWP1), secreted aspartyl proteinase (SAP4, SAP6), and morphogenesis pathway regulatory gene (EFG1) was analyzed using quantitative RT-PCR. Betamethasone and dexamethasone markedly inhibited C. albicans biofilm formation by up to 80% at a concentration of 2 mg/mL. Moreover, the inhibition of C. albicans biofilm formation was significant at concentrations ranging from 0.6 to 10 mg/mL for piroxicam and from 0.75 to 12 mg/mL for diclofenac. The expression of key genes involved in biofilm formation including EFG1, HWP1, and ALS3 was all downregulated under hyphae-inducing conditions. Moreover, the expression proteinase genes of C. albicans were upregulated following exposure with corticosteroids. The data obtained provides valuable insights into the antifungal potential of anti-inflammatory drugs. Our novel findings indicate the downregulation of several Candida genes that are crucial for morphogenesis, pathogenesis, and biofilm formation. However, further research is necessary to fully elucidate the clinical applications and effectiveness of anti-inflammatory drugs as alternative or adjunctive therapies for Candida infections.