Insights into the structure and mechanism of action of the anti-candidal lectin Mo-CBP2 and evaluation of its synergistic effect and antibiofilm activity

Plant bioactive compounds are extensively used in traditional medicine to treat diabetes, inflammation, hypertension, liver disease, and microbial infections. In this context, plant proteins are promising molecules in the treatment of candidiasis, being an alternative to the classical antifungals currently in use. This study aimed to better understand the structural characteristics of Mo -CBP 2 , a chitin-binding protein isolated from Moringa oleifera seeds. Its mode of action against Candida spp. was investigated, evaluating protein oligomerization, pore formation, secondary structure, cell wall interaction, and biofilm inhibition. Mo -CBP 2 has a trimeric and hexameric structure, which may explain its aggregation effect against Candida albicans cells. Both yeast aggregation and anti-candida activity were depleted in the presence of N,N,N′-acetylchitotriose and laminarin, indicating that Mo -CBP 2 interacts with the fungal cell wall. Mo -CBP 2 showed high stability at extreme temperatures (100 ºC) and pH (2, 4 and 10). Furthermore, treatment with Mo -CBP 2 caused pores, severe morphological damage, and the release of cytoplasmic material in Candida . Mo -CBP 2 also showed a synergistic effect with azole, polyene, and echinocandin antifungals. Finally, Mo -CBP 2 strongly inhibited biomass production in both mature and non-mature biofilms of C. albicans . This study highlights the biotechnological potential of Mo -CBP 2 as a promising anti-candida molecule against planktonic and sessile C. albicans cells. • Mo -CBP2, a protein from M. oleifera , has antifungal activity against Candida sp. • Mo- CBP2 presents a trimeric and hexameric structure, and it is highly stable. • The treatment with Mo- CBP2 caused severe damages in C. albicans cells. • The protein showed synergistic effect with antifungal drugs. • Mo- CBP2 was also active against biofilm formation and preformed biofilm.