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Article

Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus

Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Paolo Gonthier
Pathogens 2021, 10(6), 701; https://doi.org/10.3390/pathogens10060701
Received: 10 May 2021 / Revised: 24 May 2021 / Accepted: 2 June 2021 / Published: 4 June 2021
(This article belongs to the Special Issue Aspergillosis)
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. View Full-Text
Keywords: Aspergillus; triazoles; itraconazole; voriconazole; Aspergillus fumigatus; antifungal resistance; whole-genome sequencing; comparative genomics Aspergillus; triazoles; itraconazole; voriconazole; Aspergillus fumigatus; antifungal resistance; whole-genome sequencing; comparative genomics
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MDPI and ACS Style

Fan, Y.; Wang, Y.; Korfanty, G.A.; Archer, M.; Xu, J. Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus. Pathogens 2021, 10, 701. https://doi.org/10.3390/pathogens10060701

AMA Style

Fan Y, Wang Y, Korfanty GA, Archer M, Xu J. Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus. Pathogens. 2021; 10(6):701. https://doi.org/10.3390/pathogens10060701

Chicago/Turabian Style

Fan, Yuying, Yue Wang, Gregory A. Korfanty, Meagan Archer, and Jianping Xu. 2021. "Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus" Pathogens 10, no. 6: 701. https://doi.org/10.3390/pathogens10060701

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