Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis

• Published in: Frontiers in microbiology 2023-04, Vol.14, p.1137083-1137083
• Main Authors: Sun, Liu-Liu, Li, Hao, Yan, Tian-Hua, Cao, Yong-Bing, Jiang, Yuan-Ying, Yang, Feng
• Format: Article
• Language: English
• Subjects: 5-flucytosine; aneuploidy; Candida parapsilosis; caspofungin; cross tolerance; Microbiology
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2023.1137083

is an emerging major human fungal pathogen. Echinocandins are first-line antifungal drugs for the treatment of invasive infections. In clinical isolates, tolerance to echinocandins in species is mostly due to point mutations of genes, which encode the target protein of echinocandins. However, here, we found chromosome 5 trisomy was the major mechanism of adaptation to the echinocandin drug caspofungin, and mutations were rare events. Chromosome 5 trisomy conferred tolerance to echinocandin drugs caspofungin and micafungin and cross-tolerance to 5-flucytosine, another class of antifungal drugs. The inherent instability of aneuploidy caused unstable drug tolerance. Tolerance to echinocandins might be due to increased copy number and expression of , which encodes chitin synthase. Although copy number of chitinase genes and was also increased to the trisomic level, the expression was buffered to the disomic level. Tolerance to 5-flucytosine might be due to the decreased expression of . Therefore, the pleiotropic effect of aneuploidy on antifungal tolerance was due to the simultaneous regulation of genes on the aneuploid chromosome and genes on euploid chromosomes. In summary, aneuploidy provides a rapid and reversible mechanism of drug tolerance and cross-tolerance in .