Azole Resistance in Candida parapsilosis From Patients With Burns in Mexico: A Genomic and Phylogenetic Analysis

Candida species are common causes of nosocomial infections. Candida parapsilosis has emerged as an important pathogen. Mortality rates associated with invasive C. parapsilosis infections range from 14.5% to 47%, with azole resistance estimated between 4% and 15%. Resistance mechanisms include mutations in ERG11 that diminish azole binding, upregulation of ergosterol biosynthesis genes due to mutations in regulatory factors like UPC2 and NDT80, and increased efflux pump activity.

Thirty clinical strains of the C. parapsilosis complex were isolated from bloodstream cultures, biopsies and catheter tips from hospitalised patients from a major rehabilitation centre in Mexico between June 2011 and August 2016. Minimum inhibitory concentrations for fluconazole, voriconazole, itraconazole, caspofungin, micafungin, anidulafungin and amphotericin B were determined using the broth microdilution method. Whole genome sequencing was conducted using Illumina technology, with subsequent assembly and annotation. Analyses included antifungal resistance variant screening, SNP distance, average nucleotide identity and phylogenetic comparisons with publicly available genomes.

Most strains (96.7%, 29/30) were identified as C. parapsilosis sensu stricto, predominantly isolated from blood. Thirty-three percent of isolates showed phenotypic resistance to fluconazole. The SNP-distance and maximum-likelihood phylogenetic analyses revealed two distinct haplotypes and the genotype 1: ERG11^WT/Y132F, CDR1^{I1287V/I1287V} and UPC2^WT/N455D was the most represented (8/10 isolates).

C. parapsilosis sensu stricto was the predominant species isolated, with a notable proportion exhibiting resistance to FLU and VOR. The Y132F variant in the ERG11 gene was present in most sequenced isolates.