Beyond colonization: Candida albicans exhibits substantial pathogenic potential in cystic fibrosis environments.

Cystic fibrosis (CF) sputum represents a highly permissive niche for microbial colonization, yet the contribution of Candida albicans to disease progression remains insufficiently investigated despite its frequent detection in CF airways. We hypothesized that the heterogeneous nature of CF lung, reflected through the emergence of oxygen-depleted niches during disease progression, modulates C. albicans pathogenicity and antifungal susceptibility. Using complementary in vitro and in vivo approaches, we show that clinical CF isolates of C. albicans are virulent in CF-mimicking environments. Synthetic CF medium (SCFM2) supported robust filamentation, with oxygen-nutrient interplay critically shaping fungal growth and drug response. In a novel CF infection model using zebrafish morphants, we observed heightened susceptibility to C. albicans compared to wild-type embryos. Reporter strains showed elevated ECE1 expression, indicating increased candidalysin production and virulence in vivo. Our study provides compelling evidence that CF isolates of C. albicans have pathogenic potential, warranting consideration in future therapeutic strategies.