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Analysis of clinical Candida parapsilosis isolates reveals copy number variation in key fluconazole resistance genes.

Authors :
Bergin S
Doorley LA
Rybak JM
Wolfe KH
Butler G
Cuomo CA
Rogers PD
Source :
BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 14. Date of Electronic Publication: 2023 Dec 14.
Publication Year :
2023

Abstract

We used whole-genome sequencing to analyse a collection of 35 fluconazole resistant and 7 susceptible Candida parapsilosis isolates 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, ERG11 and CDR1B , in resistant isolates. Two strains have a CNV at the ERG11 locus; the entire ORF is amplified in one, and only the promoter region is amplified in the other. We show the annotated telomeric gene CDR1B is actually an artefactual in silico fusion of two highly similar neighbouring CDR genes due to an assembly error in the C. parapsilosis CDC317 reference genome. We report highly variable copy numbers of the CDR1B region 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 the CDR gene family in the C. parapsilosis species complex, showing that it is a highly dynamic family.

Details

Language :
English
ISSN :
2692-8205
Database :
MEDLINE
Journal :
BioRxiv : the preprint server for biology
Accession number :
38168157
Full Text :
https://doi.org/10.1101/2023.12.13.571446