Targeting Yeast Pathogens with Lectins: A Narrative Review from Mechanistic Insights to the Need for Addressing Translational Challenges

Diseases associated with yeast pathogens have become an increasingly serious global health issue. The range of virulence factors and the development of mechanisms of resistance have posed a significant challenge in the fight against these types of infections. Lectins, proteins capable of reversibly binding to carbohydrates and glycoconjugates, have been assessed as antifungal agents. This review shows that lectins have demonstrated versatility and significant potential as therapeutic agents against <i>Candida</i>, <i>Nakaseomyces</i> and <i>Cryptococcus</i>. These molecules act through diverse mechanisms, including disruption of fungal cell membranes, induction of oxidative stress, inhibition of ergosterol biosynthesis, and interference with mitochondrial and lysosomal functions. Some lectins have been shown to inhibit yeast-to-hyphae morphological transitions and biofilm formation, which are critical virulence factors for pathogenic yeasts. Moreover, some lectins have shown potential to enhance the efficacy of conventional antifungal drugs through synergistic interactions, though these effects can depend on the fungal isolate. Beyond in vitro activity, translational considerations remain underdeveloped in the context of antifungal applications of lectins. Some lectins exhibit minimal toxicity, while others require careful dosing due to potential toxicity or undesired immunogenicity. Delivery and stability also present challenges, though strategies such as chemical modifications and topical, mucosal, or nanoparticle-based formulations show promise. Overall, the multifaceted antifungal activities of lectins highlight their promising role as innovative candidates in the development of novel therapies to address the growing challenge of yeast pathogen resistance. However, significant knowledge gaps persist, highlighting the urgent need for coordinated research that bridges in vitro findings with practical pharmacological applications.