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Genetic Analyses of Amphotericin B Susceptibility in Aspergillus fumigatus

Aspergillus fumigatus is a ubiquitous saprophytic mold that can cause a range of clinical syndromes, from allergic reactions to invasive infections. Amphotericin B (AMB) is a polyene antifungal drug that has been used to treat a broad range of systemic mycoses since 1958, including as a primary trea...

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Autores principales: Fan, Yuying, Korfanty, Gregory A., Xu, Jianping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538161/
https://www.ncbi.nlm.nih.gov/pubmed/34682281
http://dx.doi.org/10.3390/jof7100860
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author Fan, Yuying
Korfanty, Gregory A.
Xu, Jianping
author_facet Fan, Yuying
Korfanty, Gregory A.
Xu, Jianping
author_sort Fan, Yuying
collection PubMed
description Aspergillus fumigatus is a ubiquitous saprophytic mold that can cause a range of clinical syndromes, from allergic reactions to invasive infections. Amphotericin B (AMB) is a polyene antifungal drug that has been used to treat a broad range of systemic mycoses since 1958, including as a primary treatment option against invasive aspergillosis in regions with high rates (≥10%) of environmental triazole resistance. However, cases of AMB-resistant A. fumigatus strains have been increasingly documented over the years, and high resistance rates were recently reported in Brazil and Canada. The objective of this study is to identify candidate mutations associated with AMB susceptibility using a genome-wide association analysis of natural strains, and to further investigate a subset of the mutations in their putative associations with differences in AMB minimum inhibitory concentration (MIC) and in growths at different AMB concentrations through the analysis of progeny from a laboratory genetic cross. Together, our results identified a total of 34 candidate single-nucleotide polymorphisms (SNPs) associated with AMB MIC differences—comprising 18 intergenic variants, 14 missense variants, one synonymous variant, and one non-coding transcript variant. Importantly, progeny from the genetic cross allowed us to identify putative SNP–SNP interactions impacting progeny growth at different AMB concentrations.
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spelling pubmed-85381612021-10-24 Genetic Analyses of Amphotericin B Susceptibility in Aspergillus fumigatus Fan, Yuying Korfanty, Gregory A. Xu, Jianping J Fungi (Basel) Article Aspergillus fumigatus is a ubiquitous saprophytic mold that can cause a range of clinical syndromes, from allergic reactions to invasive infections. Amphotericin B (AMB) is a polyene antifungal drug that has been used to treat a broad range of systemic mycoses since 1958, including as a primary treatment option against invasive aspergillosis in regions with high rates (≥10%) of environmental triazole resistance. However, cases of AMB-resistant A. fumigatus strains have been increasingly documented over the years, and high resistance rates were recently reported in Brazil and Canada. The objective of this study is to identify candidate mutations associated with AMB susceptibility using a genome-wide association analysis of natural strains, and to further investigate a subset of the mutations in their putative associations with differences in AMB minimum inhibitory concentration (MIC) and in growths at different AMB concentrations through the analysis of progeny from a laboratory genetic cross. Together, our results identified a total of 34 candidate single-nucleotide polymorphisms (SNPs) associated with AMB MIC differences—comprising 18 intergenic variants, 14 missense variants, one synonymous variant, and one non-coding transcript variant. Importantly, progeny from the genetic cross allowed us to identify putative SNP–SNP interactions impacting progeny growth at different AMB concentrations. MDPI 2021-10-14 /pmc/articles/PMC8538161/ /pubmed/34682281 http://dx.doi.org/10.3390/jof7100860 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
Korfanty, Gregory A.
Xu, Jianping
Genetic Analyses of Amphotericin B Susceptibility in Aspergillus fumigatus
title Genetic Analyses of Amphotericin B Susceptibility in Aspergillus fumigatus
title_full Genetic Analyses of Amphotericin B Susceptibility in Aspergillus fumigatus
title_fullStr Genetic Analyses of Amphotericin B Susceptibility in Aspergillus fumigatus
title_full_unstemmed Genetic Analyses of Amphotericin B Susceptibility in Aspergillus fumigatus
title_short Genetic Analyses of Amphotericin B Susceptibility in Aspergillus fumigatus
title_sort genetic analyses of amphotericin b susceptibility in aspergillus fumigatus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538161/
https://www.ncbi.nlm.nih.gov/pubmed/34682281
http://dx.doi.org/10.3390/jof7100860
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