Title : Limonene inhibits virulence related traits in Candida albicans
Abstract:
Multidrug resistance and high toxicity towards conventional antifungal drugs is causing serious concern worldwide. Exploration of novel compounds with immense therapeutic potential is required. The present study evaluates the antifungal potential of limonene, a secondary metabolite found in several citrus plants based essential oils. In-vitro anti-Candida studies were performed including haemolysis assay, antifungal susceptibility, secretion of hydrolytic enzymes, morphological transition, adhesion and biofilm formation. Further validation was done by in-silico studies using docking tools followed by MD simulations with five major virulence associated antifungal targets (Als3, Bcr1, Plb1, Sap2 and Tec1). With MIC of 300 μg/ml, it causes only 1% RBC cell lysis. Limonene significantly reduced adhesion to buccal epithelial cells. At MIC, hydrolytic enzymes proteinases and phospholipases was also reduced by 73% and 53% respectively. Limonene treatment inhibits morphological transition in C. albicans which was monitored microscopically. Adhesion and biofilm formation was also reduced by 91% and 87% respectively. Docking and MD simulation studies confirm stable hydrophobic interactions with all the target proteins except Bcr1. Present study suggests that limonene inhibits major virulence factors in C. albicans. Due to low toxicity, easy availability and high antifungal potential, limonene is a suitable candidate to be explored as an antifungal drug. Present work needs to be corroborated with molecular and in vivo studies to understand its mode of action and exact target sites.
