Clearing <i>Candida</i> biofilms using combined antimicrobial Sophorolipids with Amphotericin B and Itraconazole

Candida albicans biofilms present a major clinical challenge due to their resistance to conventional antifungal therapies. Sophorolipids (SLs), glycolipid biosurfactants produced by Starmerella riodocensis, have emerged as promising antifungal agents. This study evaluates SLs produced using soybean meal, a low-cost agro-industrial substrate, for antibiofilm activity and synergistic potential with amphotericin B (AmB) and itraconazole (ITZ), two widely used antifungals. Both crude and purified SLs reduced biofilm formation and metabolic activity, with purified SLs showing superior efficacy. SLs reduced the amount of AmB required to achieve up to 90% biofilm inhibition. SL-ITZ combinations also showed enhanced antibiofilm activity, indicating synergy across distinct antifungal classes. Given the amphiphilic nature of SLs and the central role of adhesion, hyphal development, and morphogenesis in biofilm formation, we hypothesized that SLs interfere with key virulence-associated processes. Accordingly, qRT-PCR analysis demonstrated significant downregulation of ALS3, HWP1, and CDC28 under hyphal-inducing conditions. Cytotoxicity assessment using SLs, representing a conservative evaluation, showed no significant toxicity to mammalian cells. Collectively, these findings highlight soybean meal-derived SLs as effective and safe adjuncts to conventional antifungal therapy for combating drug-resistant C. albicans biofilms.