Susceptibility to Medium-Chain Fatty Acids Is Associated with Trisomy of Chromosome 7 in .

Fatty acids have known antifungal effects and are used in over-the-counter topical treatments. Screening of a collection of gene knockouts in revealed that one strain, carrying a deletion of the transcription factor , is very susceptible to the medium-chain fatty acid undecanoic acid. However, reintroducing does not restore resistance, and editing in a different background does not introduce sensitivity. Whole-genome sequencing revealed that the 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 strain SN152, used to delete and many other genes, has undergone a major loss of heterozygosity event on chromosome 2 and a smaller one on chromosome 3. Aneuploidy (changes in chromosome number) and loss of heterozygosity (LOH) occur frequently in the human-pathogenic yeast 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 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.