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 Candida 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: Candida albicans, Candida parapsilosis and Candida tropicalis. Growing biofilms were exposed to etomidate at 31.25–500 µg ml−1. Then, an ALS3 adhesive protein from C. albicans 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 C. albicans, C. parapsilosis and C. tropicalis 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 C. albicans. These results revealed that etomidate inhibited the growth of biofilms.

Promising activity of etomidate against mixed biofilms of fluconazole-resistant Candida albicans and methicillin-resistant Staphylococcus aureus

“…In a previous study, Do Av Sá et al . [15] observed that etomidate exhibited promising activity against the formation of biofilms of fluconazole-resistant C. albicans . Molecular docking experiments demonstrated that etomidate attaches to the same region of the ALS3 complex ligand (heptathreonine), and was close to the residues of the catalytic triad (Ser170) and to the amino acid residue, which had an adhesion function (Lys59).…”

“…Etomidate has reported activity against biofilms of fluconazole-resistant C. albicans [14,15] and MRSA [16]. However, there is no description of its activity against polymicrobial biofilms.…”

Sertraline has in vitro activity against both mature and forming biofilms of different Candida species

“…Scanning electron microscopy (SEM) was used to better visualize the effect of SER on microscopic biofilm structures [16]. The C. auris strain was chosen as representative because of its clinical relevance.…”

“…The biofilm preventive effect of SER was evaluated according to Xie et al [15] and Sá et al [16], with modifications. Briefly, the microorganisms were prepared as described in the previous section, then the inoculum (100 µl) was added to each well of 96-well plates and incubated for different times (6, 12, 24 and 48 h) at 35 °C together with 100 µl SER at different concentrations (MIC/2, MIC, 2×MIC, 4×MIC and 8×MIC for each strain) diluted in RPMI 1640 in order to evaluate the time that each SER concentration starts to be effective in inhibiting the number of metabolically active cells in the biofilm.…”

Drug Repurposing in Medical Mycology: Identification of Compounds as Potential Antifungals to Overcome the Emergence of Multidrug-Resistant Fungi

“…The hypnotic agent, etomidate, works against the biofilm of fluconazole-resistant Candida spp. strains [109]. The antiseptic alexidine [103] and the finasteride used to treat the prostatic hyperplasia [110] were highly active in vitro at preventing C. albicans biofilms.…”