Candida albicans genome adaptation in azole resistant isolates from autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) patients

Chronic mucocutaneous candidosis due to Candida albicans is frequent in patients with autoimmune polyendocrinopathy candidosis ectodermal dystrophy (APECED). These patients require lifelong antifungal treatment with azoles which might result in the emergence of azole-resistant C. albicans isolates. However, the molecular mechanisms that allow C. albicans to cause disease and adapt to antifungal treatment in these patients in vastly unknown. Here we comparatively analysed the genome sequences and antifungal susceptibility profile of 14 C. albicans isolates from the oral cavities of five APECED patients. 14/13 C. albicans isolates showed reduced-susceptibly or resistance to fluconazole. Phylogenetic analyses demonstrated that all APECED isolates from individual patients arose from patient-specific lineages. Single nucleotide variants in genes related to homologous DNA repair mechanisms such as meiosis were associated with APECED (p <0.0001). Altogether our data demonstrates that antifungal adaptation of C. albicans in APECED patients might be associated with polymorphisms in proteins responsible for maintaining DNA repair mechanisms. ImportanceChronic mucocutaneous canididosis (CMC) caused by Candida albicans is common in patients with primary immunodeficiencies such as autoimmune polyendocrinopathy candidosis ectodermal dystrophy (APECED). These patients receive to long-term antifungal therapy thus promoting the emergence of antifungal resistance. Our knowledge about the mechanisms facilitating CMC in patients with APECED is very limited. Here we demonstrated that most C. albicans isolates from patients with CMC are resistant to azoles and that polymorphisms in genes responsible for maintaining DNA repair mechanisms might facilitate infection.