Withania somnifera seed oil exhibits antibiofilm properties against drug-resistant Candida auris clinical isolate through modulation in cell permeability

Abstract

Aim

Candida auris, fast evolving drug-resistant fungus, poses an imminent global health threat. Alternative drug-resistance nonevoking treatment options are necessary. This study explored the antifungal and antibiofilm efficacies of Withania somnifera seed oil extracted using super critical CO₂ (WSSO) against clinically isolated Fluconazole-resistant C. auris and its putative mode-of-action.

Methods and Results

Effects of WSSO on C. auris were tested by broth microdilution method, with observed IC₅₀ at 5.96 mg ml⁻¹. Time-kill assay revealed that WSSO is fungistatic. Mechanistically, ergosterol binding and sorbitol protection assays showed that C. auris cell membrane and cell wall are the targets for WSSO. Lactophenol: Cotton-Blue: Trypan-Blue staining confirmed loss of intracellular contents by WSSO treatment. Candida auris biofilm formation was disrupted by WSSO (BIC₅₀: 8.52 mg ml⁻¹). Additionally, WSSO exhibited dose and time-dependent mature biofilm eradication property with 50% efficacies at 23.27, 19.28, 18.18, and 7.22 mg ml⁻¹ over 24, 48, 72, and 96 h, respectively. Biofilm eradication by WSSO was further substantiated through scanning electron microscopy. Standard-of-Care Amphotericin B, at its break-point concentration, (2 μg ml⁻¹) was found to be inefficient as an antibiofilm agent.

Conclusions

WSSO is a potent antifungal agent effective against planktonic C. auris and its biofilm.

fluconazole-resistant Candida auris, Withania somnifera seed oil, WSSO, antifungal–fungistatic activity, ergosterol binding, sorbitol protection, time-kill, antibiofilm activity, scanning electron microscopy