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Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus
Aspergillus fumigatus is a ubiquitous fungus and the main agent of aspergillosis, a common fungal infection in the immunocompromised population. Triazoles such as itraconazole and voriconazole are the common first-line drugs for treating aspergillosis. However, triazole resistance in A. fumigatus ha...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227032/ https://www.ncbi.nlm.nih.gov/pubmed/34199862 http://dx.doi.org/10.3390/pathogens10060701 |
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author | Fan, Yuying Wang, Yue Korfanty, Gregory A. Archer, Meagan Xu, Jianping |
author_facet | Fan, Yuying Wang, Yue Korfanty, Gregory A. Archer, Meagan Xu, Jianping |
author_sort | Fan, Yuying |
collection | PubMed |
description | Aspergillus fumigatus is a ubiquitous fungus and the main agent of aspergillosis, a common fungal infection in the immunocompromised population. Triazoles such as itraconazole and voriconazole are the common first-line drugs for treating aspergillosis. However, triazole resistance in A. fumigatus has been reported in an increasing number of countries. While most studies of triazole resistance have focused on mutations in the triazole target gene cyp51A, >70% of triazole-resistant strains in certain populations showed no mutations in cyp51A. To identify potential non-cyp51A mutations associated with triazole resistance in A. fumigatus, we analyzed the whole genome sequences and triazole susceptibilities of 195 strains from 12 countries. These strains belonged to three distinct clades. Our genome-wide association study (GWAS) identified a total of six missense mutations significantly associated with itraconazole resistance and 18 missense mutations with voriconazole resistance. In addition, to investigate itraconazole and pan-azole resistance, Fisher’s exact tests revealed 26 additional missense variants tightly linked to the top 20 SNPs obtained by GWAS, of which two were consistently associated with triazole resistance. The large number of novel mutations related to triazole resistance should help further investigations into their molecular mechanisms, their clinical importance, and the development of a comprehensive molecular diagnosis toolbox for triazole resistance in A. fumigatus. |
format | Online Article Text |
id | pubmed-8227032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82270322021-06-26 Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus Fan, Yuying Wang, Yue Korfanty, Gregory A. Archer, Meagan Xu, Jianping Pathogens Article Aspergillus fumigatus is a ubiquitous fungus and the main agent of aspergillosis, a common fungal infection in the immunocompromised population. Triazoles such as itraconazole and voriconazole are the common first-line drugs for treating aspergillosis. However, triazole resistance in A. fumigatus has been reported in an increasing number of countries. While most studies of triazole resistance have focused on mutations in the triazole target gene cyp51A, >70% of triazole-resistant strains in certain populations showed no mutations in cyp51A. To identify potential non-cyp51A mutations associated with triazole resistance in A. fumigatus, we analyzed the whole genome sequences and triazole susceptibilities of 195 strains from 12 countries. These strains belonged to three distinct clades. Our genome-wide association study (GWAS) identified a total of six missense mutations significantly associated with itraconazole resistance and 18 missense mutations with voriconazole resistance. In addition, to investigate itraconazole and pan-azole resistance, Fisher’s exact tests revealed 26 additional missense variants tightly linked to the top 20 SNPs obtained by GWAS, of which two were consistently associated with triazole resistance. The large number of novel mutations related to triazole resistance should help further investigations into their molecular mechanisms, their clinical importance, and the development of a comprehensive molecular diagnosis toolbox for triazole resistance in A. fumigatus. MDPI 2021-06-04 /pmc/articles/PMC8227032/ /pubmed/34199862 http://dx.doi.org/10.3390/pathogens10060701 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fan, Yuying Wang, Yue Korfanty, Gregory A. Archer, Meagan Xu, Jianping Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus |
title | Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus |
title_full | Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus |
title_fullStr | Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus |
title_full_unstemmed | Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus |
title_short | Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus |
title_sort | genome-wide association analysis for triazole resistance in aspergillus fumigatus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227032/ https://www.ncbi.nlm.nih.gov/pubmed/34199862 http://dx.doi.org/10.3390/pathogens10060701 |
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