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 non-evoking treatment options are necessary. This study explored the antifungal and anti-biofilm 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 was 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. C. 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 (SEM). Standard-of-Care Amphotericin B, at its break-point concentration, (2 µg ml−1) was found to be inefficient as an anti-biofilm agent. Conclusions WSSO is a potent antifungal agent effective against planktonic C. auris and its biofilm.

Current Perspectives of Antifungal Therapy: A Special Focus on Candida auris

“…Its mechanism of action was associated with disturbing the membrane integrity of C. auris cells, evidenced through ergosterol binding and sorbitol protection assays. However, the seed oil was inactive against the mature biofilm formed by C. auris [ 57 ].…”