Susceptibility to Medium-Chain Fatty Acids Is Associated with Trisomy of Chromosome 7 in <i>Candida albicans</i>

Abstract

Fatty acids have known antifungal effects and are used in over-the-counter topical treatments. Screening of a collection of gene knockouts in <i>Candida albicans</i> revealed that one strain, carrying a deletion of the transcription factor <i>DAL81</i>, is very susceptible to the medium-chain fatty acid undecanoic acid. However, reintroducing <i>DAL81</i> does not restore resistance, and editing <i>DAL81</i> in a different background does not introduce sensitivity. Whole-genome sequencing revealed that the <i>C. albicans</i><i>dal81Δ/Δ</i> strain has an extra copy of chromosomes 5 and 7. Reversion to resistance to undecanoic acid was induced by growing the sensitive strain in yeast extract-peptone-dextrose with 60 μg/ml undecanoic acid for up to 9 days. Nine isolates that regained some resistance to undecanoic acid lost one copy of chromosome 7. The copy number of chromosome 5 does not appear to affect resistance to fatty acids. Moreover, the sensitivity may be related to having two copies of haplotype B of chromosome 7. In addition, we find that <i>C. albicans</i> strain SN152, used to delete <i>DAL81</i> and many other genes, has undergone a major loss of heterozygosity event on chromosome 2 and a smaller one on chromosome 3.<b>IMPORTANCE</b> Aneuploidy (changes in chromosome number) and loss of heterozygosity (LOH) occur frequently in the human-pathogenic yeast <i>Candida albicans</i> and are associated with adaptation to stress and to antifungal drugs. Aneuploidy and LOH can also be induced during laboratory manipulations, such as during genetic transformation. We find that <i>C. albicans</i> strain SN152, commonly used to generate gene deletions, has undergone a major LOH event on chromosome 2. One deletion strain generated in this background has acquired extra copies of chromosomes 5 and 7. We find that trisomy (three copies) of chromosome 7 is associated with sensitivity to fatty acids.