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Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis
Candida parapsilosis is an emerging major human fungal pathogen. Echinocandins are first-line antifungal drugs for the treatment of invasive Candida infections. In clinical isolates, tolerance to echinocandins in Candida species is mostly due to point mutations of FKS genes, which encode the target...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10126355/ https://www.ncbi.nlm.nih.gov/pubmed/37113223 http://dx.doi.org/10.3389/fmicb.2023.1137083 |
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author | Sun, Liu-liu Li, Hao Yan, Tian-hua Cao, Yong-bing Jiang, Yuan-ying Yang, Feng |
author_facet | Sun, Liu-liu Li, Hao Yan, Tian-hua Cao, Yong-bing Jiang, Yuan-ying Yang, Feng |
author_sort | Sun, Liu-liu |
collection | PubMed |
description | Candida parapsilosis is an emerging major human fungal pathogen. Echinocandins are first-line antifungal drugs for the treatment of invasive Candida infections. In clinical isolates, tolerance to echinocandins in Candida species is mostly due to point mutations of FKS 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 FKS 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 CHS7, which encodes chitin synthase. Although copy number of chitinase genes CHT3 and CHT4 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 FUR1. 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 C. parapsilosis. |
format | Online Article Text |
id | pubmed-10126355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101263552023-04-26 Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis Sun, Liu-liu Li, Hao Yan, Tian-hua Cao, Yong-bing Jiang, Yuan-ying Yang, Feng Front Microbiol Microbiology Candida parapsilosis is an emerging major human fungal pathogen. Echinocandins are first-line antifungal drugs for the treatment of invasive Candida infections. In clinical isolates, tolerance to echinocandins in Candida species is mostly due to point mutations of FKS 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 FKS 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 CHS7, which encodes chitin synthase. Although copy number of chitinase genes CHT3 and CHT4 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 FUR1. 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 C. parapsilosis. Frontiers Media S.A. 2023-04-11 /pmc/articles/PMC10126355/ /pubmed/37113223 http://dx.doi.org/10.3389/fmicb.2023.1137083 Text en Copyright © 2023 Sun, Li, Yan, Cao, Jiang and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Sun, Liu-liu Li, Hao Yan, Tian-hua Cao, Yong-bing Jiang, Yuan-ying Yang, Feng Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis |
title | Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis |
title_full | Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis |
title_fullStr | Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis |
title_full_unstemmed | Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis |
title_short | Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis |
title_sort | aneuploidy enables cross-tolerance to unrelated antifungal drugs in candida parapsilosis |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10126355/ https://www.ncbi.nlm.nih.gov/pubmed/37113223 http://dx.doi.org/10.3389/fmicb.2023.1137083 |
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