Candida albicans exhibits substantial genome plasticity, and such genome changes have been suggested to increase drug resistance and tolerance. Todd and Selmecki report that extensive copy number variations (CNVs) occur in the presence of azole antifungal drugs. The complex CNVs were found across the genome and amplified variable numbers of large genomic regions. They were flanked by distinct long inverted repeat sequences and included regions containing genes linked to tolerance, such as genes involved in the stress response and cell membrane integrity. Indeed, CNV formation provided increased fitness and tolerance in the presence of azoles, and no fitness costs were detected in the absence of drug. Removal of the antifungal drug led a loss of the CNVs, which suggests that transient CNV formation causes phenotypic and population-level heterogeneity observed in clinical isolates.
Todd, R. T. & Selmecki, A. Expandable and reversible copy number amplification drives rapid adaptation to antifungal drugs. eLife 9, e58349 (2020)
Berman, J. & Krysan, D. J. Drug resistance and tolerance in fungi. Nat. Rev. Microbiol. 18, 319–331 (2020)