Peroxiredoxin Asp f3 Is Essential for <named-content content-type="genus-species">Aspergillus fumigatus</named-content> To Overcome Iron Limitation during Infection

ABSTRACT 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,...

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Autores principales:	Victor Brantl, Jana M. Boysen, Annie Yap, Evgeny Golubtsov, Dominik Ruf, Thorsten Heinekamp, Maria Straßburger, Karl Dichtl, Hubertus Haas, Falk Hillmann, Johannes Wagener
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Asp f3 Aspergillus fumigatus peroxiredoxin iron regulation virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6522a73eeb674cb7804e17e5e00d975e
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spelling	oai:doaj.org-article:6522a73eeb674cb7804e17e5e00d975e2021-11-10T18:37:50ZPeroxiredoxin Asp f3 Is Essential for <named-content content-type="genus-species">Aspergillus fumigatus</named-content> To Overcome Iron Limitation during Infection10.1128/mBio.00976-212150-7511https://doaj.org/article/6522a73eeb674cb7804e17e5e00d975e2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00976-21https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Asp f3 is one of the most abundant proteins in the pathogenic mold Aspergillus fumigatus. It has an enigmatic multifaceted role as a fungal allergen, virulence factor, reactive oxygen species (ROS) scavenger, and vaccine candidate. Our study provides new insights into the cellular role of this conserved peroxiredoxin. We show that the avirulence of a Δaspf3 mutant in a murine infection model is linked to a low-iron growth defect of this mutant, which we describe for the first time. Our analyses indicated that Asp f3 is not required for maintaining iron homeostasis. Instead, we found that Asp f3 compensates for a loss of iron-dependent antioxidant enzymes. Furthermore, we identified an Asp f3-like protein which is partially functionally redundant with Asp f3. We highlight an unexpected key role of Asp f3 and its partially redundant homologue Af3l1 in overcoming the host's nutritional immunity. In addition, we uncovered a new biological role of peroxiredoxins.Victor BrantlJana M. BoysenAnnie YapEvgeny GolubtsovDominik RufThorsten HeinekampMaria StraßburgerKarl DichtlHubertus HaasFalk HillmannJohannes WagenerAmerican Society for MicrobiologyarticleAsp f3Aspergillus fumigatusperoxiredoxiniron regulationvirulenceMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Asp f3 Aspergillus fumigatus peroxiredoxin iron regulation virulence Microbiology QR1-502
spellingShingle	Asp f3 Aspergillus fumigatus peroxiredoxin iron regulation virulence Microbiology QR1-502 Victor Brantl Jana M. Boysen Annie Yap Evgeny Golubtsov Dominik Ruf Thorsten Heinekamp Maria Straßburger Karl Dichtl Hubertus Haas Falk Hillmann Johannes Wagener Peroxiredoxin Asp f3 Is Essential for <named-content content-type="genus-species">Aspergillus fumigatus</named-content> To Overcome Iron Limitation during Infection
description	ABSTRACT 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. IMPORTANCE Asp f3 is one of the most abundant proteins in the pathogenic mold Aspergillus fumigatus. It has an enigmatic multifaceted role as a fungal allergen, virulence factor, reactive oxygen species (ROS) scavenger, and vaccine candidate. Our study provides new insights into the cellular role of this conserved peroxiredoxin. We show that the avirulence of a Δaspf3 mutant in a murine infection model is linked to a low-iron growth defect of this mutant, which we describe for the first time. Our analyses indicated that Asp f3 is not required for maintaining iron homeostasis. Instead, we found that Asp f3 compensates for a loss of iron-dependent antioxidant enzymes. Furthermore, we identified an Asp f3-like protein which is partially functionally redundant with Asp f3. We highlight an unexpected key role of Asp f3 and its partially redundant homologue Af3l1 in overcoming the host's nutritional immunity. In addition, we uncovered a new biological role of peroxiredoxins.
format	article
author	Victor Brantl Jana M. Boysen Annie Yap Evgeny Golubtsov Dominik Ruf Thorsten Heinekamp Maria Straßburger Karl Dichtl Hubertus Haas Falk Hillmann Johannes Wagener
author_facet	Victor Brantl Jana M. Boysen Annie Yap Evgeny Golubtsov Dominik Ruf Thorsten Heinekamp Maria Straßburger Karl Dichtl Hubertus Haas Falk Hillmann Johannes Wagener
author_sort	Victor Brantl
title	Peroxiredoxin Asp f3 Is Essential for <named-content content-type="genus-species">Aspergillus fumigatus</named-content> To Overcome Iron Limitation during Infection
title_short	Peroxiredoxin Asp f3 Is Essential for <named-content content-type="genus-species">Aspergillus fumigatus</named-content> To Overcome Iron Limitation during Infection
title_full	Peroxiredoxin Asp f3 Is Essential for <named-content content-type="genus-species">Aspergillus fumigatus</named-content> To Overcome Iron Limitation during Infection
title_fullStr	Peroxiredoxin Asp f3 Is Essential for <named-content content-type="genus-species">Aspergillus fumigatus</named-content> To Overcome Iron Limitation during Infection
title_full_unstemmed	Peroxiredoxin Asp f3 Is Essential for <named-content content-type="genus-species">Aspergillus fumigatus</named-content> To Overcome Iron Limitation during Infection
title_sort	peroxiredoxin asp f3 is essential for <named-content content-type="genus-species">aspergillus fumigatus</named-content> to overcome iron limitation during infection
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/6522a73eeb674cb7804e17e5e00d975e
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Peroxiredoxin Asp f3 Is Essential for <named-content content-type="genus-species">Aspergillus fumigatus</named-content> To Overcome Iron Limitation during Infection

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