Genomic Insights into Azole Resistance Mechanisms in Candida tropicalis Among Hematological Malignancy Patients with Candidemia.

Abstract

Invasive candidiasis caused by Candida tropicalis poses a significant threat to patients with hematological malignancies. The increasing prevalence of azole resistance among C. tropicalis isolates complicates treatment strategies, necessitating a detailed understanding of the underlying resistance mechanisms. We conducted a genomic analysis of 15 C. tropicalis isolates collected from patients with hematological malignancies between 2017 and 2021. Whole-genome sequencing (WGS) was performed to obtain high-resolution genomic data. Three strains of C. tropicalis showed azole sensitivity in vitro susceptibility testing and the remaining 12 strains were azole resistant. MLST clade 4 emerged as the predominant azole-resistant clone. All azole-resistant isolates carried the ERG11 mutations A395T and C461T, and most carried the UPC2 mutation T503C. A consistent copy number variation (CNV) at the ERG11 locus was observed in all resistant isolates, suggesting its pivotal role in azole resistance. Our integrated analysis, including SNP, dN/dS ratio, and CNV, confirmed ERG11 as a central player in C. tropicalis' resistance mechanisms in the study. This study provides a comprehensive genomic analysis of azole-resistant C. tropicalis isolates from patients with hematological malignancies. The identification of key genomic alterations, particularly those in the ERG11 gene, offers valuable insights for clinical management and underscores the need for continuous resistant gene surveillance to guide antifungal stewardship in oncology settings.