Phenotypic Alterations Linked to Virulence and Pathogenicity in the Saprotrophic Candida haemulonii Complex Induced by Amoeba interaction

Candida haemulonii complex (CHC) species are increasingly reported as causative agents of invasive fungal infections, with concerning patterns of antifungal resistance and are simultaneously being isolated from diverse natural environments. These yeasts demonstrate featured adaptability and resistance across various ecological niches, particularly in their interactions with environmental micropredators such as free-living amoebae. The "amoebae training ground" hypothesis suggests that these interactions may serve as an evolutionary pressure process, where fungi that successfully evade predation develop traits that inadvertently enhance their pathogenic potential in human hosts. Our investigation into C. duobushaemulonii reveals that isolates subjected to amoebic co-culture undergo substantial adaptive changes. These adaptations include distinctive morphological transitions and phenotypic modifications that appear to enhance their survival capabilities. Most notably, these adapted strains demonstrate significantly increased virulence when tested in Galleria mellonella larvae, an established in vivo model for fungal pathogenicity. This transformation from their saprotrophic form results in enhanced pathogenic potential, suggesting that environmental pressures can drive the evolution of virulence factors in C. duobushaemulonii through specific adaptive mechanisms.