The role of DVL, a lectin from Dioclea violacea seeds, in the inhibition of Candida spp.: a study of mechanisms of action and alteration of the proteomic profile

Abstract

The growth of antifungal resistance, accelerated by decades of extensive and inappropriate use of conventional drugs, projects an alarming scenario for global health by 2050, requiring the development of innovative and effective therapeutic alternatives as soon as possible. Plant lectins have been recognized for their ability to bind to specific carbohydrates, making them potential antifungal agents. In some cases, these interactions may involve components of the fungal cell wall, resulting in changes that compromise microbial growth. In this study, we investigated the antifungal activity and mechanisms of action of a lectin obtained from Dioclea violacea (DVL) seeds against Candida albicans, Candida krusei, and Candida parapsilosis, integrating growth inhibition assays and proteomic analyses. Our findings demonstrated that DVL, through its carbohydrate recognition domain (CRD), acts to inhibit these strains via multiple mechanisms, including damage to the membrane and cell wall, dysregulation of the redox system, inhibition of ergosterol biosynthesis, and promotion of cytochrome c release. Proteomic analysis deepened our understanding of these responses, revealing changes in proteins related to cell integrity, wall remodeling, energy metabolism, drug transport, DNA repair, oxidative stress, cell defense, and cell cycle regulation. Our results highlight the complexity of fungal adaptations to treatment and identify molecular targets that may support the rational development of new therapies.