Antifungal drug adaptation in diploid and tetraploid Candida albicans

Here, we evolved diploid and tetraploid C. albicans for ~60 days in the antifungal drug caspofungin. Tetraploid-evolved lines adapted faster than diploid-evolved lines and reached higher levels of caspofungin resistance. While diploid-evolved lines generally maintained their initial genome size, tetraploid-evolved lines rapidly underwent genome-size reductions and did so prior to caspofungin adaptation. While clinical resistance was largely due to mutations in FKS1, these mutations were caused by substitutions in diploid, and indels in tetraploid isolates. Furthermore, fitness costs in the absence of drug selection were significantly less in tetraploid-evolved lines compared to the diploid-evolved lines.