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Natural compounds from freshwater mussels disrupt fungal virulence determinants and influence fluconazole susceptibility in the presence of macrophages in Cryptococcus neoformans
Summary
Researchers tested natural compounds derived from freshwater mussels against the fungal pathogen Cryptococcus neoformans and found they disrupted key virulence factors including capsule production and biofilm formation. Using proteomics analysis, they identified specific protein pathways affected by the mussel-derived compounds. The study demonstrates an anti-virulence approach that could complement existing antifungal treatments while highlighting the bioactive potential of freshwater organisms.
As the prevalence and severity of global fungal infections rise, along with an increasing incidence of antifungal resistance, new strategies to combat fungal pathogens and overcome resistance are urgently needed. Critically, our current methods to overcome fungal infections are limited and drive the evolution of resistance forward; however, an anti-virulence approach to disarm virulence factors of the pathogen and promote host cell clearance is promising. Here, we explore the efficacy of natural compounds derived from freshwater mussels against classical fungal virulence determinants, including thermotolerance, capsule production, stress response, and biofilm formation. We integrate our phenotypic discoveries with state-of-the-art mass spectrometry-based proteomics to identify mechanistic drivers of these antifungal properties and propose innovative avenues to reduce infection and support the treatment of resistant strains.