Exposure of Aspergillus fumigatus to Atorvastatin Leads to Altered Membrane Permeability and Induction of an Oxidative Stress Response
| Autor: | Gerard Sheehan, Kevin Kavanagh, Ahmad Ajdidi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Microbiology (medical)
Statin Membrane permeability medicine.drug_class Atorvastatin Plant Science Pharmacology medicine.disease_cause aspergillus Article Aspergillus fumigatus 03 medical and health sciences chemistry.chemical_compound proteomics Heat shock protein medicine lcsh:QH301-705.5 Ecology Evolution Behavior and Systematics 030304 developmental biology 0303 health sciences biology Gliotoxin ergosterol 030306 microbiology Glutathione atorvastatin biology.organism_classification infection Aspergillus chemistry lcsh:Biology (General) lipids (amino acids peptides and proteins) Oxidative stress medicine.drug |
| Zdroj: | Journal of Fungi Journal of Fungi, Vol 6, Iss 2, p 42 (2020) Volume 6 Issue 2 |
| ISSN: | 2309-608X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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