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Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis
Candida species are the most common human fungal pathogens worldwide. Although C. albicans remains the predominant cause of candidiasis, infections caused by non-albicans Candida species, including C. parapsilosis, are increasing. In C. albicans, genome plasticity has been shown to be a prevalent st...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510177/ https://www.ncbi.nlm.nih.gov/pubmed/34612700 http://dx.doi.org/10.1128/Spectrum.00508-21 |
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author | Yang, Feng Lu, Hui Wu, Hao Fang, Ting Berman, Judith Jiang, Yuan-ying |
author_facet | Yang, Feng Lu, Hui Wu, Hao Fang, Ting Berman, Judith Jiang, Yuan-ying |
author_sort | Yang, Feng |
collection | PubMed |
description | Candida species are the most common human fungal pathogens worldwide. Although C. albicans remains the predominant cause of candidiasis, infections caused by non-albicans Candida species, including C. parapsilosis, are increasing. In C. albicans, genome plasticity has been shown to be a prevalent strategy of adaptation to stresses. However, the role of aneuploidy in C. parapsilosis is largely unknown. In this study, we found that six different aneuploid karyotypes conferred adaptation to the endoplasmic reticulum stress inducer tunicamycin (TUN) in C. parapsilosis. Interestingly, a specific aneuploidy including trisomy of chromosome 6 (Chr6x3) also enabled cross-tolerance to aureobasidin A (AbA), a sphingolipid biosynthesis inhibitor. Consistent with this, selection on AbA identified adaptors with three different aneuploid karyotypes, including Chr6x3, which also enabled cross-tolerance to both AbA and TUN. Therefore, as in other Candida species, recurrent aneuploid karyotypes enable the adaptation of C. parapsilosis to specific stresses, and specific aneuploidies enable cross-adaptation to different stresses. IMPORTANCE Candida parapsilosis is an emerging human fungal pathogen, especially prevalent in neonates. Aneuploidy, having uneven numbers of chromosomes, is a well-known mechanism for adapting to stress in Candida albicans, the most common human fungal pathogen. In this study, we exposed C. parapsilosis to two very different drugs and selected for rare cells that grew in one of the drugs. We found that the majority of isolates that grew in the drugs had acquired an extra copy of one of several aneuploid chromosomes and that specific aneuploid chromosomes appeared in several independent cell clones. Importantly, an extra copy of chromosome 6 was detected following selection in either one of the drugs, and this extra chromosome conferred the ability to grow in both drugs, a property called cross-adaptation, or cross-tolerance. Thus, this study highlights the genome plasticity of C. parapsilosis and the ability of an extra copy of a single chromosome to promote cell growth in the presence of more than one drug. |
format | Online Article Text |
id | pubmed-8510177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-85101772021-11-08 Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis Yang, Feng Lu, Hui Wu, Hao Fang, Ting Berman, Judith Jiang, Yuan-ying Microbiol Spectr Research Article Candida species are the most common human fungal pathogens worldwide. Although C. albicans remains the predominant cause of candidiasis, infections caused by non-albicans Candida species, including C. parapsilosis, are increasing. In C. albicans, genome plasticity has been shown to be a prevalent strategy of adaptation to stresses. However, the role of aneuploidy in C. parapsilosis is largely unknown. In this study, we found that six different aneuploid karyotypes conferred adaptation to the endoplasmic reticulum stress inducer tunicamycin (TUN) in C. parapsilosis. Interestingly, a specific aneuploidy including trisomy of chromosome 6 (Chr6x3) also enabled cross-tolerance to aureobasidin A (AbA), a sphingolipid biosynthesis inhibitor. Consistent with this, selection on AbA identified adaptors with three different aneuploid karyotypes, including Chr6x3, which also enabled cross-tolerance to both AbA and TUN. Therefore, as in other Candida species, recurrent aneuploid karyotypes enable the adaptation of C. parapsilosis to specific stresses, and specific aneuploidies enable cross-adaptation to different stresses. IMPORTANCE Candida parapsilosis is an emerging human fungal pathogen, especially prevalent in neonates. Aneuploidy, having uneven numbers of chromosomes, is a well-known mechanism for adapting to stress in Candida albicans, the most common human fungal pathogen. In this study, we exposed C. parapsilosis to two very different drugs and selected for rare cells that grew in one of the drugs. We found that the majority of isolates that grew in the drugs had acquired an extra copy of one of several aneuploid chromosomes and that specific aneuploid chromosomes appeared in several independent cell clones. Importantly, an extra copy of chromosome 6 was detected following selection in either one of the drugs, and this extra chromosome conferred the ability to grow in both drugs, a property called cross-adaptation, or cross-tolerance. Thus, this study highlights the genome plasticity of C. parapsilosis and the ability of an extra copy of a single chromosome to promote cell growth in the presence of more than one drug. American Society for Microbiology 2021-10-06 /pmc/articles/PMC8510177/ /pubmed/34612700 http://dx.doi.org/10.1128/Spectrum.00508-21 Text en Copyright © 2021 Yang et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Yang, Feng Lu, Hui Wu, Hao Fang, Ting Berman, Judith Jiang, Yuan-ying Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis |
title | Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis |
title_full | Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis |
title_fullStr | Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis |
title_full_unstemmed | Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis |
title_short | Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis |
title_sort | aneuploidy underlies tolerance and cross-tolerance to drugs in candida parapsilosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510177/ https://www.ncbi.nlm.nih.gov/pubmed/34612700 http://dx.doi.org/10.1128/Spectrum.00508-21 |
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