Journal
SCIENCE
Volume 313, Issue 5785, Pages 367-370Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1128242
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Funding
- NIAID NIH HHS [R01 AI062427] Funding Source: Medline
- NIDCR NIH HHS [DE10641-S] Funding Source: Medline
- PHS HHS [R01 AIO62427] Funding Source: Medline
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Resistance to the limited number of available antifungal drugs is a serious problem in the treatment of Candida albicans. We found that aneuploidy in general and a specific segmental aneuploidy, consisting of an isochromosome composed of the two left arms of chromosome 5, were associated with azole resistance. The isochromosome forms around a single centromere flanked by an inverted repeat and was found as an independent chromosome or fused at the telomere to a full-length homolog of chromosome 5. Increases and decreases in drug resistance were strongly associated with gain and loss of this isochromosome, which bears genes expressing the enzyme in the ergosterol pathway targeted by azole drugs, efflux pumps, and a transcription factor that positively regulates a subset of efflux pump genes.
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