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Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage
The activity of fumagillin, a mycotoxin produced by Aspergillus fumigatus, has not been studied in depth. In this study, we used a commercial fumagillin on cultures of two cell types (A549 pneumocytes and RAW 264.7 macrophages). This toxin joins its target, MetAP2 protein, inside cells and, as a res...
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/PMC8619997/ https://www.ncbi.nlm.nih.gov/pubmed/34829223 http://dx.doi.org/10.3390/jof7110936 |
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author | Guruceaga, Xabier Perez-Cuesta, Uxue Pellon, Aize Cendon-Sanchez, Saioa Pelegri-Martinez, Eduardo Gonzalez, Oskar Hernando, Fernando Luis Mayayo, Emilio Anguita, Juan Alonso, Rosa M. Keller, Nancy P. Ramirez-Garcia, Andoni Rementeria, Aitor |
author_facet | Guruceaga, Xabier Perez-Cuesta, Uxue Pellon, Aize Cendon-Sanchez, Saioa Pelegri-Martinez, Eduardo Gonzalez, Oskar Hernando, Fernando Luis Mayayo, Emilio Anguita, Juan Alonso, Rosa M. Keller, Nancy P. Ramirez-Garcia, Andoni Rementeria, Aitor |
author_sort | Guruceaga, Xabier |
collection | PubMed |
description | The activity of fumagillin, a mycotoxin produced by Aspergillus fumigatus, has not been studied in depth. In this study, we used a commercial fumagillin on cultures of two cell types (A549 pneumocytes and RAW 264.7 macrophages). This toxin joins its target, MetAP2 protein, inside cells and, as a result, significantly reduces the electron chain activity, the migration, and the proliferation ability on the A549 cells, or affects the viability and proliferation ability of the RAW 264.7 macrophages. However, the toxin stimulates the germination and double branch hypha production of fungal cultures, pointing out an intrinsic resistant mechanism to fumagillin of fungal strains. In this study, we also used a fumagillin non-producer A. fumigatus strain (∆fmaA) as well as its complemented strain (∆fmaA::fmaA) and we tested the fumagillin secretion of the fungal strains using an Ultra High-Performance Liquid Chromatography (UHPLC) method. Furthermore, fumagillin seems to protect the fungus against phagocytosis in vitro, and during in vivo studies using infection of immunosuppressed mice, a lower fungal burden in the lungs of mice infected with the ∆fmaA mutant was demonstrated. |
format | Online Article Text |
id | pubmed-8619997 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86199972021-11-27 Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage Guruceaga, Xabier Perez-Cuesta, Uxue Pellon, Aize Cendon-Sanchez, Saioa Pelegri-Martinez, Eduardo Gonzalez, Oskar Hernando, Fernando Luis Mayayo, Emilio Anguita, Juan Alonso, Rosa M. Keller, Nancy P. Ramirez-Garcia, Andoni Rementeria, Aitor J Fungi (Basel) Article The activity of fumagillin, a mycotoxin produced by Aspergillus fumigatus, has not been studied in depth. In this study, we used a commercial fumagillin on cultures of two cell types (A549 pneumocytes and RAW 264.7 macrophages). This toxin joins its target, MetAP2 protein, inside cells and, as a result, significantly reduces the electron chain activity, the migration, and the proliferation ability on the A549 cells, or affects the viability and proliferation ability of the RAW 264.7 macrophages. However, the toxin stimulates the germination and double branch hypha production of fungal cultures, pointing out an intrinsic resistant mechanism to fumagillin of fungal strains. In this study, we also used a fumagillin non-producer A. fumigatus strain (∆fmaA) as well as its complemented strain (∆fmaA::fmaA) and we tested the fumagillin secretion of the fungal strains using an Ultra High-Performance Liquid Chromatography (UHPLC) method. Furthermore, fumagillin seems to protect the fungus against phagocytosis in vitro, and during in vivo studies using infection of immunosuppressed mice, a lower fungal burden in the lungs of mice infected with the ∆fmaA mutant was demonstrated. MDPI 2021-11-03 /pmc/articles/PMC8619997/ /pubmed/34829223 http://dx.doi.org/10.3390/jof7110936 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 Guruceaga, Xabier Perez-Cuesta, Uxue Pellon, Aize Cendon-Sanchez, Saioa Pelegri-Martinez, Eduardo Gonzalez, Oskar Hernando, Fernando Luis Mayayo, Emilio Anguita, Juan Alonso, Rosa M. Keller, Nancy P. Ramirez-Garcia, Andoni Rementeria, Aitor Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage |
title | Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage |
title_full | Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage |
title_fullStr | Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage |
title_full_unstemmed | Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage |
title_short | Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage |
title_sort | aspergillus fumigatus fumagillin contributes to host cell damage |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619997/ https://www.ncbi.nlm.nih.gov/pubmed/34829223 http://dx.doi.org/10.3390/jof7110936 |
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