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Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection

Aspergillus fumigatus is an important fungal pathogen that causes allergic reactions but also life-threatening infections. One of the most abundant A. fumigatus proteins is Asp f3. This peroxiredoxin is a major fungal allergen and known for its role as a virulence factor, vaccine candidate, and scav...

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Autores principales: Brantl, Victor, Boysen, Jana M., Yap, Annie, Golubtsov, Evgeny, Ruf, Dominik, Heinekamp, Thorsten, Straßburger, Maria, Dichtl, Karl, Haas, Hubertus, Hillmann, Falk, Wagener, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406167/
https://www.ncbi.nlm.nih.gov/pubmed/34399627
http://dx.doi.org/10.1128/mBio.00976-21
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author Brantl, Victor
Boysen, Jana M.
Yap, Annie
Golubtsov, Evgeny
Ruf, Dominik
Heinekamp, Thorsten
Straßburger, Maria
Dichtl, Karl
Haas, Hubertus
Hillmann, Falk
Wagener, Johannes
author_facet Brantl, Victor
Boysen, Jana M.
Yap, Annie
Golubtsov, Evgeny
Ruf, Dominik
Heinekamp, Thorsten
Straßburger, Maria
Dichtl, Karl
Haas, Hubertus
Hillmann, Falk
Wagener, Johannes
author_sort Brantl, Victor
collection PubMed
description Aspergillus fumigatus is an important fungal pathogen that causes allergic reactions but also life-threatening infections. One of the most abundant A. fumigatus proteins is Asp f3. This peroxiredoxin is a major fungal allergen and known for its role as a virulence factor, vaccine candidate, and scavenger of reactive oxygen species. Based on the hypothesis that Asp f3 protects A. fumigatus against killing by immune cells, we investigated the susceptibility of a conditional aspf3 mutant by employing a novel assay. Surprisingly, Asp f3-depleted hyphae were killed as efficiently as the wild type by human granulocytes. However, we identified an unexpected growth defect of mutants that lack Asp f3 under low-iron conditions, which explains the avirulence of the Δaspf3 deletion mutant in a murine infection model. A. fumigatus encodes two Asp f3 homologues which we named Af3l (Asp f3-like) 1 and Af3l2. Inactivation of Af3l1, but not of Af3l2, exacerbated the growth defect of the conditional aspf3 mutant under iron limitation, which ultimately led to death of the double mutant. Inactivation of the iron acquisition repressor SreA partially compensated for loss of Asp f3 and Af3l1. However, Asp f3 was not required for maintaining iron homeostasis or siderophore biosynthesis. Instead, we show that it compensates for a loss of iron-dependent antioxidant enzymes. Iron supplementation restored the virulence of the Δaspf3 deletion mutant in a murine infection model. Our results unveil the crucial importance of Asp f3 to overcome nutritional immunity and reveal a new biological role of peroxiredoxins in adaptation to iron limitation.
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spelling pubmed-84061672021-09-09 Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection Brantl, Victor Boysen, Jana M. Yap, Annie Golubtsov, Evgeny Ruf, Dominik Heinekamp, Thorsten Straßburger, Maria Dichtl, Karl Haas, Hubertus Hillmann, Falk Wagener, Johannes mBio Research Article Aspergillus fumigatus is an important fungal pathogen that causes allergic reactions but also life-threatening infections. One of the most abundant A. fumigatus proteins is Asp f3. This peroxiredoxin is a major fungal allergen and known for its role as a virulence factor, vaccine candidate, and scavenger of reactive oxygen species. Based on the hypothesis that Asp f3 protects A. fumigatus against killing by immune cells, we investigated the susceptibility of a conditional aspf3 mutant by employing a novel assay. Surprisingly, Asp f3-depleted hyphae were killed as efficiently as the wild type by human granulocytes. However, we identified an unexpected growth defect of mutants that lack Asp f3 under low-iron conditions, which explains the avirulence of the Δaspf3 deletion mutant in a murine infection model. A. fumigatus encodes two Asp f3 homologues which we named Af3l (Asp f3-like) 1 and Af3l2. Inactivation of Af3l1, but not of Af3l2, exacerbated the growth defect of the conditional aspf3 mutant under iron limitation, which ultimately led to death of the double mutant. Inactivation of the iron acquisition repressor SreA partially compensated for loss of Asp f3 and Af3l1. However, Asp f3 was not required for maintaining iron homeostasis or siderophore biosynthesis. Instead, we show that it compensates for a loss of iron-dependent antioxidant enzymes. Iron supplementation restored the virulence of the Δaspf3 deletion mutant in a murine infection model. Our results unveil the crucial importance of Asp f3 to overcome nutritional immunity and reveal a new biological role of peroxiredoxins in adaptation to iron limitation. American Society for Microbiology 2021-08-17 /pmc/articles/PMC8406167/ /pubmed/34399627 http://dx.doi.org/10.1128/mBio.00976-21 Text en Copyright © 2021 Brantl et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Brantl, Victor
Boysen, Jana M.
Yap, Annie
Golubtsov, Evgeny
Ruf, Dominik
Heinekamp, Thorsten
Straßburger, Maria
Dichtl, Karl
Haas, Hubertus
Hillmann, Falk
Wagener, Johannes
Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection
title Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection
title_full Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection
title_fullStr Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection
title_full_unstemmed Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection
title_short Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection
title_sort peroxiredoxin asp f3 is essential for aspergillus fumigatus to overcome iron limitation during infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406167/
https://www.ncbi.nlm.nih.gov/pubmed/34399627
http://dx.doi.org/10.1128/mBio.00976-21
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