Genomic Plasticity and Drug Resistance in Fungal Pathogens

Genomic plasticity in fungal pathogens encompasses dynamic processes—such as chromosomal rearrangements, copy number variation and heterozygosity shifts—that enable rapid adaptation to environmental stresses including antifungal exposure. Aneuploidy and segmental duplications often arise under drug pressure, altering gene dosage to promote tolerance or resistance to azoles, echinocandins and polyenes. Loss of heterozygosity can unmask recessive resistance alleles, while parasexual cycles and gene flow between clonal lineages introduce novel combinations of adaptive traits. Drug concentration gradients further influence evolutionary trajectories, with subinhibitory levels favouring step‐wise mutational changes and supra‐inhibitory stresses selecting for tolerance via aneuploid karyotypes. Recognising the global burden of invasive fungal infections, a nuanced understanding of these genomic responses is essential to inform therapeutic strategies and mitigate the spread of drug‐resistant strains.

Research from Nature Portfolio

A comprehensive genomic survey of over 180 clinical isolates of Candida albicans has revealed a predominantly clonal population structure interspersed with evidence of gene flow between distinct lineages. This study demonstrated that, alongside clonal expansion, recombination and parasexual processes contribute to lineage diversification. Certain clonal clusters exhibited pseudogenisation in key virulence genes, suggesting niche adaptation, while secondary recombination events facilitated the distribution of beneficial alleles across the population. These findings establish that both clonality and regulated genetic exchange underpin the evolutionary potential of this major human fungal pathogen, emphasising the importance of population-level genetic diversity in the emergence of drug-resistant traits.

Genomic Plasticity and Drug Resistance in Fungal Pathogens publication trend

The graph below shows the total number of articles in genomic plasticity and drug resistance in fungal pathogens across all publications each year (not limited to Nature Index journals).

Technical terms

Aneuploidy: Variation in chromosome number from the normal complement, influencing gene dosage.

Copy Number Variation (CNV): Gain or loss of DNA segments that alter the number of copies of genes or genomic regions.

Loss of Heterozygosity (LOH): Genomic event in which one allele of a gene is lost, unmasking recessive traits.

Minimal Inhibitory Concentration (MIC50): Drug concentration that reduces growth by 50% in a microbial population.

Drug Tolerance: Phenotype where subpopulations grow slowly above the MIC without stable resistance mutations.

References

1. Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in Candida albicans. Molecular Biology and Evolution (2023).
2. Step-wise evolution of azole resistance through copy number variation followed by KSR1 loss of heterozygosity in Candida albicans. PLOS Pathogens (2024).
3. Antifungal Tolerance and Resistance Emerge at Distinct Drug Concentrations and Rely upon Different Aneuploid Chromosomes. mBio (2023).
4. Gene flow contributes to diversification of the major fungal pathogen Candida albicans. Nature Communications (2018).
5. The Parasexual Cycle in Candida albicans Provides an Alternative Pathway to Meiosis for the Formation of Recombinant Strains. PLOS Biology (2008).