Genomic characterization of Candida parapsilosis hospital isolates revealed the spread and persistence of a fluconazole-resistant cluster associated with increased erg11 copies

Candida parapsilosis is one of the most common species associated with candidemia infections globally. Recently, the emergence of fluconazole-resistant C. parapsilosis has become a significant global public health concern. In this study, we investigated the genomic epidemiology and potential mechanisms of antifungal resistance among 51 hospital isolates in Qatar. Whole-genome single nucleotide polymorphism (SNP) analysis revealed evidence for cross-hospital transmission and the presence of 5 major clades, with clade I mainly consists of fluconazole resistant (FLU-R) isolates between 2015-2021. However, none of these FLU-R isolates carried signature mutations in common loci associated with azole resistance such as erg11, erg6, and tac1. Instead, almost all FLU-R isolates analysed here had elevated copy number of erg11, ranging from 4-9 copies per diploid genome. Genome-wide association study indicated that several mutations in als3 were significantly linked to resistance to FLU, 5-flucytosine and amphotericin B. Notably, all clade I isolates had a unique mutation in efg1, which has an important role in biofilm formation, indicating these isolates may have greater propensity to form biofilm and cause clonal transmission than isolates in other genetic clusters, and to persist within hospitals for prolonged period.