Potential Antifungal Activity of Retinoids Against Non-albicans Candida Species

Non-albicans Candida (NAC) species have emerged as significant opportunistic pathogens due to their reduced susceptibility to antifungal agents combined with their strong ability to form biofilms. The severity of systemic candidiasis caused by NAC species highlights the need for novel antifungal strategies. Retinoids, a group of compounds derived from vitamin A, have been demonstrated to possess significant antifungal activity against the reference strain C. albicans ATCC 2091. This study aimed to assess the antifungal potential of three retinoids, all-trans retinoic acid (ATRA), trifarotene, and tazarotene, against NAC clinical isolates. Various concentrations of the retinoids (from 1 mM to 0.06 mM) were tested in vitro against the growth, adhesion, and biofilm development of NAC species, including Candida glabrata, Candida krusei, and Candida tropicalis, as well as a reference strain of C. auris (CDC B11903). At 1 mM, all three compounds maximally inhibited the growth, adhesion, and biofilm formation of all tested NAC species. At lower concentrations (0.5-0.06 mM), C. krusei remained the most susceptible, especially to tazarotene. Tazarotene also showed a strong inhibitory effect on C. auris and C. glabrata at 0.5-0.25 mM; however, this effect was weaker than that observed against C. krusei. At low concentrations (0.12-0.06 mM), only trifarotene induced a mild but statistically significant inhibition of C. tropicalis growth. Trifarotene at 0.5 mM was also the most effective retinoid in inhibiting C. glabrata and C. tropicalis adherence and biofilm formation, with inhibitory activity maintained even at sub-0.5 mM concentrations (0.25-0.12 mM). Overall, the results suggest that all three retinoids exhibited dose-dependent and species-specific antifungal activity against NAC species, supporting their potential as novel, tailored antifungal agents against drug-resistant Candida strains.