<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...

Descripción completa

Guardado en:
Detalles Bibliográficos
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:
Acceso en línea:https://doaj.org/article/e06448526b3e4decb5db64303b6d2e08
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario: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.