Hotspot mutations and genomic expansion of ERG11 are major mechanisms of azole resistance in environmental and human commensal isolates of Candida tropicalis

Hu, Tianren; Wang, Sijia; Bing, Jian; Zheng, Qiushi; Du, Han; Li, Chao; Guan, Zhangyue; Bai, Feng-yan; Nobile, Clarissa J.; Chu, Haiqing; Huang, Guanghua

doi:10.1016/j.ijantimicag.2023.107010

Cited by 2 publications

References 38 publications

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

Bergin,

Doorley,

Rybak

et al. 2023

Preprint

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We 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.

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

Bergin,

Doorley,

Rybak

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

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

Bergin,

Doorley,

Rybak

et al. 2024

Antimicrob Agents Chemother

View full text Add to dashboard Cite

We used whole-genome sequencing to analyze 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 persistent clinical lineages were identified. We identified copy number variation (CNV) 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 that the annotated telomeric gene CDR1B is actually an artifactual in silico fusion of two highly similar neighboring 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 the 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.

show abstract

Hotspot mutations and genomic expansion of ERG11 are major mechanisms of azole resistance in environmental and human commensal isolates of Candida tropicalis

Cited by 2 publications

References 38 publications

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

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

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

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