Emergence of Flucytosine-Resistant Candida tropicalis Clade, the Netherlands

This is the authors' abstract. We don't add key points for this paper.

Candida tropicalis is the second most virulent Candida species after C. albicans. Previous studies from the Netherlands and France reported a notable reduction in susceptibility to flucytosine (5-FC) in a substantial proportion of C. tropicalis isolates. We investigated epidemiologic patterns of C. tropicalis isolates in the Netherlands and the genetic mechanisms driving widespread non-wild-type (WT) 5-FC resistance. We conducted antifungal susceptibility testing and used advanced molecular techniques, including short tandem repeat genotyping and whole-genome sequencing paired with single-nucleotide polymorphism analysis, to analyze 250 C. tropicalis isolates collected across the Netherlands during 2012-2022. Our findings revealed the rapid emergence of a 5-FC-resistant, non-WT C. tropicalis clade, accounting for >40% of all C. tropicalis isolates by 2022. Genomic analysis identified a homozygous nonsense mutation in the FCY2 gene, which was exclusive to this non-WT population. Continued surveillance efforts are needed to detect and prevent the spread of drug-resistant Candida species.