<i>Aspergillus fumigatus</i> Fumagillin Contributes to Host Cell Damage

The activity of fumagillin, a mycotoxin produced by <i>Aspergillus fumigatus</i>, 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...

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Autores principales:	Xabier Guruceaga, Uxue Perez-Cuesta, Aize Pellon, Saioa Cendon-Sanchez, Eduardo Pelegri-Martinez, Oskar Gonzalez, Fernando Luis Hernando, Emilio Mayayo, Juan Anguita, Rosa M. Alonso, Nancy P. Keller, Andoni Ramirez-Garcia, Aitor Rementeria
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	fumagillin <i>Aspergillus fumigatus</i> virulence factor pathogenesis RAW 264.7 A549 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e06448526b3e4decb5db64303b6d2e08
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spelling	oai:doaj.org-article:e06448526b3e4decb5db64303b6d2e082021-11-25T18:05:57Z<i>Aspergillus fumigatus</i> Fumagillin Contributes to Host Cell Damage10.3390/jof71109362309-608Xhttps://doaj.org/article/e06448526b3e4decb5db64303b6d2e082021-11-01T00:00:00Zhttps://www.mdpi.com/2309-608X/7/11/936https://doaj.org/toc/2309-608XThe activity of fumagillin, a mycotoxin produced by <i>Aspergillus fumigatus</i>, 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 <i>A. fumigatus</i> strain (∆<i>fmaA</i>) as well as its complemented strain (∆<i>fmaA::fmaA)</i> 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 ∆<i>fmaA</i> mutant was demonstrated.Xabier GuruceagaUxue Perez-CuestaAize PellonSaioa Cendon-SanchezEduardo Pelegri-MartinezOskar GonzalezFernando Luis HernandoEmilio MayayoJuan AnguitaRosa M. AlonsoNancy P. KellerAndoni Ramirez-GarciaAitor RementeriaMDPI AGarticlefumagillin<i>Aspergillus fumigatus</i>virulence factorpathogenesisRAW 264.7A549Biology (General)QH301-705.5ENJournal of Fungi, Vol 7, Iss 936, p 936 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fumagillin <i>Aspergillus fumigatus</i> virulence factor pathogenesis RAW 264.7 A549 Biology (General) QH301-705.5
spellingShingle	fumagillin <i>Aspergillus fumigatus</i> virulence factor pathogenesis RAW 264.7 A549 Biology (General) QH301-705.5 Xabier Guruceaga Uxue Perez-Cuesta Aize Pellon Saioa Cendon-Sanchez Eduardo Pelegri-Martinez Oskar Gonzalez Fernando Luis Hernando Emilio Mayayo Juan Anguita Rosa M. Alonso Nancy P. Keller Andoni Ramirez-Garcia Aitor Rementeria <i>Aspergillus fumigatus</i> Fumagillin Contributes to Host Cell Damage
description	The activity of fumagillin, a mycotoxin produced by <i>Aspergillus fumigatus</i>, 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 <i>A. fumigatus</i> strain (∆<i>fmaA</i>) as well as its complemented strain (∆<i>fmaA::fmaA)</i> 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 ∆<i>fmaA</i> mutant was demonstrated.
format	article
author	Xabier Guruceaga Uxue Perez-Cuesta Aize Pellon Saioa Cendon-Sanchez Eduardo Pelegri-Martinez Oskar Gonzalez Fernando Luis Hernando Emilio Mayayo Juan Anguita Rosa M. Alonso Nancy P. Keller Andoni Ramirez-Garcia Aitor Rementeria
author_facet	Xabier Guruceaga Uxue Perez-Cuesta Aize Pellon Saioa Cendon-Sanchez Eduardo Pelegri-Martinez Oskar Gonzalez Fernando Luis Hernando Emilio Mayayo Juan Anguita Rosa M. Alonso Nancy P. Keller Andoni Ramirez-Garcia Aitor Rementeria
author_sort	Xabier Guruceaga
title	<i>Aspergillus fumigatus</i> Fumagillin Contributes to Host Cell Damage
title_short	<i>Aspergillus fumigatus</i> Fumagillin Contributes to Host Cell Damage
title_full	<i>Aspergillus fumigatus</i> Fumagillin Contributes to Host Cell Damage
title_fullStr	<i>Aspergillus fumigatus</i> Fumagillin Contributes to Host Cell Damage
title_full_unstemmed	<i>Aspergillus fumigatus</i> Fumagillin Contributes to Host Cell Damage
title_sort	<i>aspergillus fumigatus</i> fumagillin contributes to host cell damage
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e06448526b3e4decb5db64303b6d2e08
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<i>Aspergillus fumigatus</i> Fumagillin Contributes to Host Cell Damage

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