A sunflower mannose-binding lectin: antifungal effect on Candida albicans

REGENTE, MARIANA

Congreso; 6 th Latin American Glycobiology Congress; 2021

Sociedad Latinoamericana de Glicobiología

Candida infections are a major health concern due to the increasing emergence of antifungal resistant strains. Hence, the search for new antifungal agents offers a promising opportunity for improving the treatment strategies against candidiasis. We have characterized a sunflower mannose-binding lectin called Helja and demonstrated its antifungal activity against Candida spp. The aim of the current presentation was to show the update of our work about the mechanism of action of Helja and its ability to inhibit Candida albicans biofilm development and adherence to buccal epithelial cells. In addition, we have evaluated the combined effect of Helja with fluconazole (FLC). Our results showed that C. albicans cells treated with 0.1 μg/μl of Helja exhibited a drastic decrease in yeast survival. The lectin affected the fungal cell integrity, induced the production of hydrogen peroxide and inhibited the morphological transition from yeast to filamentous forms. Helja caused a significant reduction of adherent cells and a decrease in biofilm biomass and coverage area developed on polystyrene microplates. The treatment with the protein also reduced the surface hydrophobicity of fungal cells. We show the binding of Helja-FITC to yeast cells and this interaction was displaced by mannose and Concanavalin A, suggesting the interaction of Helja with the mannoproteins of Candida albicans cell wall. Thus, the binding Helja-Candida also provides a possible explanation of the lectin effect on cell adherence, biofilm development and cellular surface hydrophobicity, relevant features related to virulence of the pathogen. On the other hand, the Helja+FLC combination exhibited an inhibitory effect of fungal growth about three times greater than the sum of both compounds separately. In addition, cells treated with Helja+FLC showed differentials morphological alterations compared to treatment with Helja or FLC alone, such as loss of the typical oval form of yeast, nucleus disintegration and formation of multimera structures. Our findings suggest that while Helja targets the cell wall and destabilizes the plasma membrane, it also facilitates the action of FLC on the cell membrane. 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.