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Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus

Siderophores play an important role in fungal virulence, serving as trackers for in vivo imaging and as biomarkers of fungal infections. However, siderophore uptake is only partially characterized. As the major cause of aspergillosis, Aspergillus fumigatus is one of the most common airborne fungal p...

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Autores principales: Aguiar, Mario, Orasch, Thomas, Shadkchan, Yana, Caballero, Patricia, Pfister, Joachim, Sastré-Velásquez, Luis Enrique, Gsaller, Fabio, Decristoforo, Clemens, Osherov, Nir, Haas, Hubertus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600649/
https://www.ncbi.nlm.nih.gov/pubmed/36125294
http://dx.doi.org/10.1128/mbio.02192-22
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author Aguiar, Mario
Orasch, Thomas
Shadkchan, Yana
Caballero, Patricia
Pfister, Joachim
Sastré-Velásquez, Luis Enrique
Gsaller, Fabio
Decristoforo, Clemens
Osherov, Nir
Haas, Hubertus
author_facet Aguiar, Mario
Orasch, Thomas
Shadkchan, Yana
Caballero, Patricia
Pfister, Joachim
Sastré-Velásquez, Luis Enrique
Gsaller, Fabio
Decristoforo, Clemens
Osherov, Nir
Haas, Hubertus
author_sort Aguiar, Mario
collection PubMed
description Siderophores play an important role in fungal virulence, serving as trackers for in vivo imaging and as biomarkers of fungal infections. However, siderophore uptake is only partially characterized. As the major cause of aspergillosis, Aspergillus fumigatus is one of the most common airborne fungal pathogens of humans. Here, we demonstrate that this mold species mediates the uptake of iron chelated by the secreted siderophores triacetylfusarinine C (TAFC) and fusarinine C by the major facilitator-type transporters MirB and MirD, respectively. In a murine aspergillosis model, MirB but not MirD was found to be crucial for virulence, indicating that TAFC-mediated uptake plays a dominant role during infection. In the absence of MirB, TAFC becomes inhibitory by decreasing iron availability because the mutant is not able to recognize iron that is chelated by TAFC. MirB-mediated transport was found to tolerate the conjugation of fluorescein isothiocyanate to triacetylfusarinine C, which might aid in the development of siderophore-based antifungals in a Trojan horse approach, particularly as the role of MirB in pathogenicity restrains its mutational inactivation. Taken together, this study identified the first eukaryotic siderophore transporter that is crucial for virulence and elucidated its translational potential as well as its evolutionary conservation.
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spelling pubmed-96006492022-10-27 Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus Aguiar, Mario Orasch, Thomas Shadkchan, Yana Caballero, Patricia Pfister, Joachim Sastré-Velásquez, Luis Enrique Gsaller, Fabio Decristoforo, Clemens Osherov, Nir Haas, Hubertus mBio Research Article Siderophores play an important role in fungal virulence, serving as trackers for in vivo imaging and as biomarkers of fungal infections. However, siderophore uptake is only partially characterized. As the major cause of aspergillosis, Aspergillus fumigatus is one of the most common airborne fungal pathogens of humans. Here, we demonstrate that this mold species mediates the uptake of iron chelated by the secreted siderophores triacetylfusarinine C (TAFC) and fusarinine C by the major facilitator-type transporters MirB and MirD, respectively. In a murine aspergillosis model, MirB but not MirD was found to be crucial for virulence, indicating that TAFC-mediated uptake plays a dominant role during infection. In the absence of MirB, TAFC becomes inhibitory by decreasing iron availability because the mutant is not able to recognize iron that is chelated by TAFC. MirB-mediated transport was found to tolerate the conjugation of fluorescein isothiocyanate to triacetylfusarinine C, which might aid in the development of siderophore-based antifungals in a Trojan horse approach, particularly as the role of MirB in pathogenicity restrains its mutational inactivation. Taken together, this study identified the first eukaryotic siderophore transporter that is crucial for virulence and elucidated its translational potential as well as its evolutionary conservation. American Society for Microbiology 2022-09-20 /pmc/articles/PMC9600649/ /pubmed/36125294 http://dx.doi.org/10.1128/mbio.02192-22 Text en Copyright © 2022 Aguiar 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
Aguiar, Mario
Orasch, Thomas
Shadkchan, Yana
Caballero, Patricia
Pfister, Joachim
Sastré-Velásquez, Luis Enrique
Gsaller, Fabio
Decristoforo, Clemens
Osherov, Nir
Haas, Hubertus
Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus
title Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus
title_full Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus
title_fullStr Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus
title_full_unstemmed Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus
title_short Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus
title_sort uptake of the siderophore triacetylfusarinine c, but not fusarinine c, is crucial for virulence of aspergillus fumigatus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600649/
https://www.ncbi.nlm.nih.gov/pubmed/36125294
http://dx.doi.org/10.1128/mbio.02192-22
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