Analysis of clinicalCandida parapsilosisisolates reveals copy number variation in key fluconazole resistance genes

Abstract

AbstractWe used whole-genome sequencing to analyse a collection of 35 fluconazole resistant and 7 susceptibleCandida parapsilosisisolates together with coverage analysis and GWAS techniques to identify new mechanisms of fluconazole resistance. Phylogenetic analysis shows that although the collection is diverse, two probable outbreak groups were identified. We identified copy number variation of two genes,ERG11andCDR1B, in resistant isolates. Two strains have a CNV at theERG11locus; the entire ORF is amplified in one, and only the promoter region is amplified in the other. We show the annotated telomeric geneCDR1Bis actually an artefactualin silicofusion of two highly similar neighbouringCDRgenes due to an assembly error in theC. parapsilosisCDC317 reference genome. We report highly variable copy numbers of theCDR1Bregion across the collection. Several strains have increased expansion of the two genes into a tandem array of new chimeric genes. Other strains have experienced a deletion between the two genes creating a single gene with a reciprocal chimerism. We find translocations, duplications, and gene conversion across theCDRgene family in theC. parapsilosisspecies complex, showing that it is a highly dynamic family.