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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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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. |
format | Online Article Text |
id | pubmed-9600649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
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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