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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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