Sophorolipid-Drug Combination: A Promising Approach to Mitigate Antimicrobial Resistance and Modulate Pathogen-
Drug Interactions in Candida albicans Biofilm Formation

Antimicrobial resistance has emerged as a significant global threat, demanding innovative strategies to combat drug-resistant pathogens. Candida albicans, a prevalent fungal pathogen, exhibits increasing resistance to conventional antifungals. This study investigates the potential approach, combining sophorolipid (SL) with clinical antifungal drugs, to combat resistance and alter pathogen-drug interactions in C. albicans. SL exhibits potential antibiofilm activity against both young & preformed biofilms at
biofilm inhibitory concentration (BIC50) at 750 mg/L & 2048 mg/L respectively. It also showed 50% reduced metabolic activity at 512 mg/L and 1024 mg/L. The combination of SL with fluconazole decreased the BIC50 from 128 mg/L to 64 mg/L. For preformed biofilms, SL was effective at 256 mg/L. SL combined with ketoconazole improved its effectiveness by 2-fold at 16 mg/L. The itraconazole combination showed a 4-fold improvement in antibiofilm activity compared to single treatments with a BIC50 value at 4 mg/L while reducing SL concentrations by 2-fold. In fact, it showed a 50% decrease in metabolic activity at 2 mg/L. Amphotericin B showed synergy with SL at 1 mg/L and 0.5 mg/L for antibiofilm and reduced metabolic activity, respectively. In conclusion, harnessing the synergistic effects of this combination could pave the way for the development of more effective antifungal therapies to address the global challenge of drug resistance.