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Exposure of Aspergillus fumigatus to Atorvastatin Leads to Altered Membrane Permeability and Induction of an Oxidative Stress Response

Aspergillus fumigatus is a serious cause of disease in immune-deficient patients and in those with pulmonary malfunction (e.g., cystic fibrosis (CF), asthma). Atorvastatin is a member of the statin drug family, which are the main therapeutic agents used to decrease high serum cholesterol levels by i...

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Autores principales: Ajdidi, Ahmad, Sheehan, Gerard, Kavanagh, Kevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344724/
https://www.ncbi.nlm.nih.gov/pubmed/32225059
http://dx.doi.org/10.3390/jof6020042
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author Ajdidi, Ahmad
Sheehan, Gerard
Kavanagh, Kevin
author_facet Ajdidi, Ahmad
Sheehan, Gerard
Kavanagh, Kevin
author_sort Ajdidi, Ahmad
collection PubMed
description Aspergillus fumigatus is a serious cause of disease in immune-deficient patients and in those with pulmonary malfunction (e.g., cystic fibrosis (CF), asthma). Atorvastatin is a member of the statin drug family, which are the main therapeutic agents used to decrease high serum cholesterol levels by inhibiting (HMG-CoA) reductase enzyme. The aim of the work presented here was to analyse the antifungal activity of atorvastatin and assess its effect on the virulence of A. fumigatus. Atorvastatin demonstrated strong antifungal activity and reduced the growth and viability of A. fumigatus. Exposure of A. fumigatus to atorvastatin led to a reduction in ergosterol content and increased membrane permeability, as evidenced by the release of protein, amino acids and gliotoxin. Proteomic analysis revealed an increased abundance of proteins associated with an oxidative stress response, such as the glutathione s-transferase family protein (+8.43-fold), heat shock protein Hsp30/Hsp42 (+2.02-fold) and 5-demethoxyubiquinone hydroxylase, mitochondrial (+1.73-fold), as well as secondary metabolites such as isocyanide synthase A icsA (+8.52-fold) and non-ribosomal peptide synthetase fmpE (+3.06-fold). The results presented here indicate that atorvastatin has strong antifungal properties and may have potential application in the treatment of A. fumigatus infections alone or in combination with existing antifungal agents.
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spelling pubmed-73447242020-07-09 Exposure of Aspergillus fumigatus to Atorvastatin Leads to Altered Membrane Permeability and Induction of an Oxidative Stress Response Ajdidi, Ahmad Sheehan, Gerard Kavanagh, Kevin J Fungi (Basel) Article Aspergillus fumigatus is a serious cause of disease in immune-deficient patients and in those with pulmonary malfunction (e.g., cystic fibrosis (CF), asthma). Atorvastatin is a member of the statin drug family, which are the main therapeutic agents used to decrease high serum cholesterol levels by inhibiting (HMG-CoA) reductase enzyme. The aim of the work presented here was to analyse the antifungal activity of atorvastatin and assess its effect on the virulence of A. fumigatus. Atorvastatin demonstrated strong antifungal activity and reduced the growth and viability of A. fumigatus. Exposure of A. fumigatus to atorvastatin led to a reduction in ergosterol content and increased membrane permeability, as evidenced by the release of protein, amino acids and gliotoxin. Proteomic analysis revealed an increased abundance of proteins associated with an oxidative stress response, such as the glutathione s-transferase family protein (+8.43-fold), heat shock protein Hsp30/Hsp42 (+2.02-fold) and 5-demethoxyubiquinone hydroxylase, mitochondrial (+1.73-fold), as well as secondary metabolites such as isocyanide synthase A icsA (+8.52-fold) and non-ribosomal peptide synthetase fmpE (+3.06-fold). The results presented here indicate that atorvastatin has strong antifungal properties and may have potential application in the treatment of A. fumigatus infections alone or in combination with existing antifungal agents. MDPI 2020-03-26 /pmc/articles/PMC7344724/ /pubmed/32225059 http://dx.doi.org/10.3390/jof6020042 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ajdidi, Ahmad
Sheehan, Gerard
Kavanagh, Kevin
Exposure of Aspergillus fumigatus to Atorvastatin Leads to Altered Membrane Permeability and Induction of an Oxidative Stress Response
title Exposure of Aspergillus fumigatus to Atorvastatin Leads to Altered Membrane Permeability and Induction of an Oxidative Stress Response
title_full Exposure of Aspergillus fumigatus to Atorvastatin Leads to Altered Membrane Permeability and Induction of an Oxidative Stress Response
title_fullStr Exposure of Aspergillus fumigatus to Atorvastatin Leads to Altered Membrane Permeability and Induction of an Oxidative Stress Response
title_full_unstemmed Exposure of Aspergillus fumigatus to Atorvastatin Leads to Altered Membrane Permeability and Induction of an Oxidative Stress Response
title_short Exposure of Aspergillus fumigatus to Atorvastatin Leads to Altered Membrane Permeability and Induction of an Oxidative Stress Response
title_sort exposure of aspergillus fumigatus to atorvastatin leads to altered membrane permeability and induction of an oxidative stress response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344724/
https://www.ncbi.nlm.nih.gov/pubmed/32225059
http://dx.doi.org/10.3390/jof6020042
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