Journal Article
A Retrospective Molecular Epidemiology Study: Emergence and dissemination of Azole-Resistant Candida parapsilosis Sensu Stricto in Southern Brazil
Luiza Souza Rodrigues; Sabrina da Conceição Barbosa; Ana Paula Santiago Chacon; Adriele Celine Siqueira; Gisele Aparecida Bernardi; Marcelo Pillonetto; Vania Aparecida Vicente; Lavinia Nery Villa Stangler Arend; Terezinha Inez Estivalet Svidzinski; Libera Maria Dalla-Costa
Mycopathologia · Vol. 191, Issue 5 · 2026
Abstract
Candida parapsilosis sensu stricto has emerged as a major cause of healthcare-associated candidemia, with increasing reports of fluconazole resistance worldwide. This resistance is most commonly associated with amino acid substitutions in Erg11p, particularly Y132F; however, regional variation in resistance mechanisms and clonal dissemination remains not fully understood. This study investigated the molecular epidemiology and genomic landscape of fluconazole-resistant C. parapsilosis in Paraná, Southern Brazil, over a 10-year period. A total of 54 resistant isolates identified between 2014 and 2024 were retrospectively analyzed; 51 viable isolates were confirmed by species identification, antifungal susceptibility testing, and microsatellite genotyping. A subset of 18 representative isolates underwent whole-genome sequencing for phylogenomic analysis. Variants in genes associated with azole resistance, including ERG11 , MRR1 , TAC1 , CDR1 , MDR1 , ERG3 , and ERG6 , were characterized. Fluconazole resistance emerged in 2018 and increased thereafter. Phylogenomic analysis revealed two geographically structured lineages: a dominant clone circulating across multiple healthcare institutions in the Curitiba metropolitan area and a second lineage restricted to the northern region of the state. The dominant clone showed minimal genomic diversity (0–5 SNPs), consistent with long-term persistence. A conserved resistance profile was observed, with 17 of 18 sequenced isolates harboring the K143R substitution in Erg11p, while all retained the wild-type residue at position 132. The single isolate lacking ERG11 mutations carried a novel C849Y substitution in the Mrr1p regulator. These findings demonstrate the emergence and persistence of a highly clonal fluconazole-resistant C. parapsilosis lineage in Southern Brazil, characterized by a conserved K143R substitution independent of Y132F. The detection of closely related isolates across different hospitals underscores the need for regional genomic surveillance of hospital-adapted fungal pathogens.