“Pour some sugar on me”—Environmental Candida albicans isolates and the evolution of increased pathogenicity and antifungal resistance through sugar adaptation

Candida albicans is an opportunistic fungal pathogen that colonizes mucosal surfaces of most humans. Only in rare cases, C. albicans isolates are found in the environment. This study investigated whether environmental isolates differ in their virulence potential from clinical strains and how adaptation to a human diet influences key virulence attributes. We examined three C. albicans isolates from oak trees in the United Kingdom, and observed that one exhibited high host cell damage, increased hypha formation, invasion capacity, and candidalysin production, along with an intrinsic resistance to amphotericin B. The other two showed lower virulence which was still similar to most tested clinical isolates. All oak tree isolates showed an increased resistance to fluconazole. To mimic the more recent evolution of C. albicans to a sugar-rich diet, we evolved a low-damaging isolate in sugar-rich medium, which unexpectedly enhanced its metabolic flexibility, epithelial damage potential, and antifungal resistances, including a new resistance to amphotericin B. These findings suggest that C. albicans isolates can develop high virulence potential and antifungal resistance in the environment, and that adaptation of C. albicans to sugar-rich diets, as in westernized countries, can affect fungal pathogenicity and drug resistance.