Candida albicans cell wall phosphomannans play a role in the susceptibility to an antifungal mannose-binding lectin

DEL RÍO, MARIANELA; RADICIONI, MELISA BELÉN; MORA-MONTES, HÉCTOR M.; REGENTE, MARIANA

Virtual

Congreso; LXVI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2021

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

Candida infections constitute a threat for immunocompromised individuals, due to the limited repertoire of drugs for its efficient treatment and the increased emergence of antifungal resistant strains. We have previously isolated a sunflower mannose-binding lectin (Helja) with antifungal activity against C. albicans, which is mediated by its interaction with the outer layer of fungal cell wall enriched in mannosylated glycoproteins. This work aimed to investigate the role of the phosphomannans in mediating the fungicidal action of Helja. We have used a C. albicans glycosylation defective in cell wall phosphomannosylation (mnn4null), which is correlated with a concomitant reduction in the surface negative charge, to compare the antifungal effect of Helja relative to the wild type strain (wt). Yeast cells of both strains were incubated in the presence of Helja to follow optical reading at 630 nm and assess fungal growth. Helja inhibited mutant and wt fungal growth in 70% and 25% respectively. Microscopic analysis of the mutant yeast treated with Helja revealed the loss of cell viability and differentials morphological alterations compared to wt, such as loss of the typical oval yeast form, formation of clusters with agglutinated cells and vacuolar collapse. These results suggest that Helja could establish stronger interactions with the cell wall of the mnn4null mutants than with the wt strains, in which the presence of a greater amount of surface negative charge would display a repulsion effect with the anionic lectin (PI 4.65). In conclusion, our results provide new evidence on the nature of the molecular interactions of Helja with the outer mannoproteins and its impact on the antifungal activity, highlighting the relevance to elucidate the mode of action of new natural compounds for effective antifungal therapies design.