Molecular Epidemiology and Antifungal Susceptibility Profile of Candidozyma Isolates From Argentina.

Abstract

Background: Epidemiological surveillance of Candidozyma sp. has become important because many species of this new genus have been reported to be responsible for nosocomial outbreaks and to exhibit elevated minimal inhibitory concentrations (MIC) to one or more classes of antifungal drugs.

Objectives: To describe the genetic relationships among Argentinian clinical isolates belonging to the Candidozyma genus and to study the molecular mechanisms associated with antifungal resistance.

Methods: We performed whole-genome sequencing of 41 isolates. Identification was based on ribosomal DNA sequencing and susceptibility testing was determined according to the EUCAST document. Phylogenetic analysis, non-synonymous mutations in genes associated with antifungal resistance and the presence of copy number variations (CNVs) were investigated.

Results: We identified 12 Candidozyma haemuli, 11 Candidozyma haemuli var. vulneris, 5 Cz. haemuli/ Cz. haemuli var. vulneris ITS hybrids, 8 Candidozyma duobushaemuli and 5 Candidozyma cf. pseudohaemuli. Phylogenetic analysis, together with clinical data, demonstrated nosocomial transmission events. In addition, Cz. haemuli and Cz. haemuli var. vulneris were not separated in the phylogenetic tree; the Cz. cf. pseudohaemuli isolates clustered distantly from the Cz. pseudohaemuli type strain. Most isolates were resistant to amphotericin B, and two Cz. haemuli isolates showed fluconazole resistance and Y132F mutation in ERG11. We did not find CNV in genes associated with antifungal resistance.

Conclusions: These findings highlight the need for epidemiological surveillance of these species and the study of molecular mechanisms associated with antifungal resistance. Furthermore, we propose a taxonomic revision for Cz. haemuli var. vulneris and Cz. pseudohaemuli based on genomic data.