ArticlePLoS pathogens2024
Step-wise evolution of azole resistance through copy number variation followed by KSR1 loss of heterozygosity in Candida albicans.
Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- A multiplex droplet digital PCR assay for chromosome copy-number determination in Candida albicans.G3 (Bethesda, Md.) · 2026Article
- CRISPR-activation reveals key resistance genes and vulnerabilities of copy number variants inbioRxiv : the preprint server for biology · 2026Article
- Segmental duplications and supernumerary chromosomes drive antifungal drug resistance in Candida auris.Nature communications · 2026Article
- Micafungin exposure drives multidrug resistance inbioRxiv : the preprint server for biology · 2026Article
- Genomic hallmarks of parasexual reproduction in three hybrid groups of the human pathogenbioRxiv : the preprint server for biology · 2026Article
- Profound cell wall remodeling inMicrobiology spectrum · 2026Article
- Persistence and spread of fluconazole-resistantMicrobial genomics · 2026Article
- Article
- Stress-driven emergence of heritable non-genetic drug resistance.Research square · 2025Article
- Aneuploidy, polyploidy, and loss of heterozygosity distinguish serial bloodstream isolates ofbioRxiv : the preprint server for biology · 2025Article
- Targeted loss of heterozygosity in Candida albicans using CRISPR-Cas9 reveals the functional impact of allelic variation.Genetics · 2025Article
- Tolerance and heteroresistance to echinocandins inmSphere · 2025Review
- Hotspot gene conversion between FKS1 and FKS2 in echinocandin resistant Candida glabrata serial isolates.npj antimicrobials and resistance · 2025Article
- Understanding adaptation to fluconazole: comparative insights into tolerance and resistance inFrontiers in cellular and infection microbiology · 2025Article
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17 authors.
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Abstract
Antimicrobial drug resistance poses a global health threat, requiring a deeper understanding of the evolutionary processes that lead to its emergence in pathogens. Complex evolutionary dynamics involve multiple mutations that can result in cooperative or competitive (clonal interference) effects. Candida albicans, a major fungal pathogen, displays high rates of copy number variation (CNV) and loss of heterozygosity (LOH). CNV and LOH events involve large numbers of genes and could synergize during evolutionary adaptation. Understanding the contributions of CNV and LOH to antifungal drug adaptation is challenging, especially in the context of whole-population genome sequencing. Here, we document the sequential evolution of fluconazole tolerance and then resistance in a C. albicans isolate involving an initial CNV on chromosome 4, followed by an LOH on chromosome R that involves KSR1. Similar LOH events involving KSR1, which encodes a reductase in the sphingolipid biosynthesis pathway, were also detected in independently evolved fluconazole resistant isolates. We dissect the specific KSR1 codons that affect fluconazole resistance and tolerance. The combination of the chromosome 4 CNV and KSR1 LOH results in a >500-fold decrease in azole susceptibility relative to the progenitor, illustrating a compelling example of rapid, yet step-wise, interplay between CNV and LOH in drug resistance evolution.
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