Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

Abstract

This study evaluated the effect of etomidate against biofilms of <i>Candida</i> spp. and analysed through molecular docking the interaction of this drug with ALS3, an important protein for fungal adhesion. Three fluconazole-resistant fungi were used: <i>Candida albicans</i>, <i>Candida parapsilosis</i> and <i>Candida tropicalis</i>. Growing biofilms were exposed to etomidate at 31.25-500 µg ml^-1. Then, an ALS3 adhesive protein from <i>C. albicans</i> was analysed through a molecular mapping technique, composed of a sequence of algorithms to perform molecular mapping simulation based on classic force field theory. Etomidate showed antifungal activity against growing biofilms of resistant <i>C. albicans, C. parapsilosis</i> and <i>C. tropicalis</i> at all concentrations used in the study. The etomidate coupling analysis revealed three interactions with the residues of interest compared to hepta-threonine, which remained at the ALS3 site. In addition, etomidate decreased the expression of mannoproteins on the surface of <i>C. albicans</i>. These results revealed that etomidate inhibited the growth of biofilms.