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Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection

Hyphal growth is essential for host colonization during Aspergillus infection. The transcription factor ZfpA regulates A. fumigatus hyphal development including branching, septation, and cell wall composition. However, how ZfpA affects fungal growth and susceptibility to host immunity during infecti...

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Autores principales: Schoen, Taylor J., Calise, Dante G., Bok, Jin Woo, Giese, Morgan A., Nwagwu, Chibueze D., Zarnowski, Robert, Andes, David, Huttenlocher, Anna, Keller, Nancy P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174577/
https://www.ncbi.nlm.nih.gov/pubmed/37126504
http://dx.doi.org/10.1371/journal.ppat.1011152
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author Schoen, Taylor J.
Calise, Dante G.
Bok, Jin Woo
Giese, Morgan A.
Nwagwu, Chibueze D.
Zarnowski, Robert
Andes, David
Huttenlocher, Anna
Keller, Nancy P.
author_facet Schoen, Taylor J.
Calise, Dante G.
Bok, Jin Woo
Giese, Morgan A.
Nwagwu, Chibueze D.
Zarnowski, Robert
Andes, David
Huttenlocher, Anna
Keller, Nancy P.
author_sort Schoen, Taylor J.
collection PubMed
description Hyphal growth is essential for host colonization during Aspergillus infection. The transcription factor ZfpA regulates A. fumigatus hyphal development including branching, septation, and cell wall composition. However, how ZfpA affects fungal growth and susceptibility to host immunity during infection has not been investigated. Here, we use the larval zebrafish-Aspergillus infection model and primary human neutrophils to probe how ZfpA affects A. fumigatus pathogenesis and response to antifungal drugs in vivo. ZfpA deletion promotes fungal clearance and attenuates virulence in wild-type hosts and this virulence defect is abrogated in neutrophil-deficient zebrafish. ZfpA deletion also increases susceptibility to human neutrophils ex vivo while overexpression impairs fungal killing. Overexpression of ZfpA confers protection against the antifungal caspofungin by increasing chitin synthesis during hyphal development, while ZfpA deletion reduces cell wall chitin and increases caspofungin susceptibility in neutrophil-deficient zebrafish. These findings suggest a protective role for ZfpA activity in resistance to the innate immune response and antifungal treatment during A. fumigatus infection.
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spelling pubmed-101745772023-05-12 Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection Schoen, Taylor J. Calise, Dante G. Bok, Jin Woo Giese, Morgan A. Nwagwu, Chibueze D. Zarnowski, Robert Andes, David Huttenlocher, Anna Keller, Nancy P. PLoS Pathog Research Article Hyphal growth is essential for host colonization during Aspergillus infection. The transcription factor ZfpA regulates A. fumigatus hyphal development including branching, septation, and cell wall composition. However, how ZfpA affects fungal growth and susceptibility to host immunity during infection has not been investigated. Here, we use the larval zebrafish-Aspergillus infection model and primary human neutrophils to probe how ZfpA affects A. fumigatus pathogenesis and response to antifungal drugs in vivo. ZfpA deletion promotes fungal clearance and attenuates virulence in wild-type hosts and this virulence defect is abrogated in neutrophil-deficient zebrafish. ZfpA deletion also increases susceptibility to human neutrophils ex vivo while overexpression impairs fungal killing. Overexpression of ZfpA confers protection against the antifungal caspofungin by increasing chitin synthesis during hyphal development, while ZfpA deletion reduces cell wall chitin and increases caspofungin susceptibility in neutrophil-deficient zebrafish. These findings suggest a protective role for ZfpA activity in resistance to the innate immune response and antifungal treatment during A. fumigatus infection. Public Library of Science 2023-05-01 /pmc/articles/PMC10174577/ /pubmed/37126504 http://dx.doi.org/10.1371/journal.ppat.1011152 Text en © 2023 Schoen et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Schoen, Taylor J.
Calise, Dante G.
Bok, Jin Woo
Giese, Morgan A.
Nwagwu, Chibueze D.
Zarnowski, Robert
Andes, David
Huttenlocher, Anna
Keller, Nancy P.
Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection
title Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection
title_full Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection
title_fullStr Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection
title_full_unstemmed Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection
title_short Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection
title_sort aspergillus fumigatus transcription factor zfpa regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174577/
https://www.ncbi.nlm.nih.gov/pubmed/37126504
http://dx.doi.org/10.1371/journal.ppat.1011152
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