A plant mannose-binding lectin and fluconazole: Key targets combination against Candida albicans

Abstract

Aims: This study aimed to evaluate the combined effect of a mannose-binding lectin Helja with fluconazole (FLC) on Candida albicans and to get insights about the joint action mechanism. Methods and Results: The fungal growth was assessed following the optical density at 630 nm. Fungal cell morphology and nucleus integrity were analysed by flow cytometry and confocal laser scanning microscopy using Calcofluor White (CFW) and 4′,6-diamidino-2-phenylindole (DAPI) staining respectively. The basis of Helja + FLC action on cell wall and plasma membrane was analysed using perturbing agents. The Helja + FLC combination exhibited an inhibitory effect of fungal growth about three times greater than the sum of both compounds separately and inhibited fungal morphological plasticity, an important virulence attribute associated with drug resistance. Cells treated with Helja + FLC showed morphological changes, nucleus disintegration and formation of multimera structures, leading to cell collapse. Conclusions: Our findings indicate that the Helja + FLC combination exhibited a potent antifungal activity based on their simultaneous action on different microbial cell targets. Significance and Impact of Study: The combination of a natural protein with conventional drugs might be helpful for the design of effective therapeutic strategies against Candida, contributing to minimize the development of drug resistance and host cell toxicity.