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Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage

Authors :
Inmunología, microbiología y parasitología
Química analítica
Immunologia, mikrobiologia eta parasitologia
Kimika analitikoa
Guruceaga Sierra, Xabier
Pérez Cuesta, Uxue
Pellon Rodriguez, Aize
Cendón Sánchez, Saioa
Pelegrí Martínez, Eduardo
González Mendia, Oscar
Hernando Echevarria, Fernando Luis
Mayayo, Emilio
Anguita Castillo, Juan de Dios
Alonso Rojas, Rosa María
Keller, Nancy P.
Ramírez García, Andoni
Rementeria Ruiz, Aitor Domingo
Inmunología, microbiología y parasitología
Química analítica
Immunologia, mikrobiologia eta parasitologia
Kimika analitikoa
Guruceaga Sierra, Xabier
Pérez Cuesta, Uxue
Pellon Rodriguez, Aize
Cendón Sánchez, Saioa
Pelegrí Martínez, Eduardo
González Mendia, Oscar
Hernando Echevarria, Fernando Luis
Mayayo, Emilio
Anguita Castillo, Juan de Dios
Alonso Rojas, Rosa María
Keller, Nancy P.
Ramírez García, Andoni
Rementeria Ruiz, Aitor Domingo
Publication Year :
2021

Abstract

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.

Details

Database :
OAIster
Notes :
This research was funded by the Basque Government: grant number IT1362-19. X.G. and S.C.-S. received a Ph.D. fellowship from the Basque Government; and U.P.-C. from the University of the Basque Country., English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1286736211
Document Type :
Electronic Resource