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Overcoming Candida albicans biofilm drug resistance via azole-sophorolipid synergy.

In Scientific Reports on 21 January 2026 by Jayasekara, L. A. C. B., Watchaputi, K., et al.

Antimicrobial resistance is a momentous global threat, demanding innovative approaches to combat drug-resistant pathogens. As a prevalent fungal pathogen, Candida albicans exhibits increasing resistance to conventional antifungals, especially the azoles. This study explores a novel approach combining sophorolipids (SLs), a glycolipid biosurfactant, with clinical azoles, including fluconazole (FLZ), itraconazole (ITZ), and ketoconazole (KCZ), against C. albicans biofilms. SLs from the yeast Starmerella riodocensis exhibited promising metabolic reduction and antibiofilm activity against Candida biofilms, with a biofilm inhibitory concentration (BIC50) of 512 mg/L. Among the tested azoles, ITZ exhibited the highest antibiofilm efficacy, prompting further investigation of SLs combinations. The ITZ-SLs combination markedly enhanced antibiofilm activity against preformed biofilms, with ITZ and SLs concentrations reduced by 16-fold and 4-fold, respectively, compared with their individual treatments (achieving a BIC₅₀ of 1 mg/L ITZ and 128 mg/L SLs). Quantitative real-time polymerase chain reaction analysis revealed significant downregulation of essential biofilm-associated genes such as BCR1, EFG1, and CDC28, demonstrating SLs's ability to inhibit various stages of biofilm development and stability. Thus, the synergy observed with azole drugs, particularly ITZ and SLs, was highly effective in biofilm removal, highlighting the compatibility of anti-biofilm biosurfactant SLs with some antifungal agents.
© 2026. The Author(s).

Microbial derived-surfactants display low eco-toxicity, diverse functionality, high biodegradability, high specificity, and stability under extreme conditions. Sophorolipids are emerging as key biosurfactants of yeast origins, used in various industrial sectors to lower surface tension. Recently, sophorolipid complexes have been applied in biomedicals and agriculture to eradicate infectious problems related to human and plant fungal pathogens. This study aimed to characterize the functional properties and antifungal activities of sophorolipids produced by a newly characterized Starmerella riodocensis GT-SL1R sp. nov. strain.
Starmerella riodocensis GT-SL1R sp. nov. strain was belonged to Starmerella clade with 93.12% sequence similarity using the ITS technique for strain identification. Sophorolipids production was examined, using co-carbon substrates glucose and palm oil, with a yield on the substrate between 30 and 46%. Using shake-flasks, the S. riodocensis GT-SL1R strain produced biosurfactants with an emulsification activity of 54.59% against kerosene compared to the S. bombicola BCC5426 strain with an activity of 60.22%. Maximum productivities of GT-SL1R and the major sophorolipid-producer S. bombicola were similar at 0.8 gl-1 h-1. S. riodocensis GT-SL1R produced mixed forms of lactonic and acidic sophorolipids, shown by TCL, FTIR, and HPLC. Importantly, the complex sophorolipid mixture displayed antifungal activity against an opportunistic yeast pathogen Candida albicans by effectively reducing hyphal and biofilm formation.
Sophorolipids derived from S. riodocensis demonstrate potential industrial and biomedical applications as green surfactant and antifungal agent. Since numerous renewable bioresources and industrial wastes could be used by microbial cell factories in the biosynthesis of biosurfactants to reduce the production cost, sophorolipids hold a promising alternative to current antimicrobials in treatments against infectious diseases in humans, animals, and plants.
© 2022. The Author(s).

Melanomas account for 80% of skin cancer deaths. Due to the strong relationship between melanomas and U.V. radiation, sunscreens have been recommended for use as a primary preventative measure. However, there is a need for targeted, less invasive treatment strategies. Glycolipids such as sophorolipids and rhamnolipids are microbially derived biosurfactants possessing bioactive properties such as antimicrobial, immunomodulatory and anticancer effects. This study aimed to ascertain the differing effects of glycolipids on skin cells. Highly purified and fully characterized preparations of sophorolipids and rhamnolipids were used to treat spontaneously transformed human keratinocyte (HaCaT) and the human malignant melanocyte (SK-MEL-28) cell lines. Cell viability and morphological analyses revealed that glycolipids have differential effects on the skin cells dependent on their chemical structure. Lactonic sophorolipids and mono-rhamnolipids were shown to have a significantly detrimental effect on melanoma cell viability compared to healthy human keratinocytes. These glycolipids were shown to induce cell death via necrosis. Additionally, sophorolipids were shown to significantly inhibit SK-MEL-28 cell migration. These findings suggest that glycolipids could be used as bioactive agents with selective inhibitory effects. As such, glycolipids could be a substitute for synthetically derived surfactants in sunscreens to provide additional benefit and have the potential as novel anti-skin-cancer therapies.

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