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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-05-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011152 |
| _version_ | 1797390675747012608 |
|---|---|
| author | Taylor J Schoen Dante G Calise Jin Woo Bok Morgan A Giese Chibueze D Nwagwu Robert Zarnowski David Andes Anna Huttenlocher Nancy P Keller |
| author_facet | Taylor J Schoen Dante G Calise Jin Woo Bok Morgan A Giese Chibueze D Nwagwu Robert Zarnowski David Andes Anna Huttenlocher Nancy P Keller |
| author_sort | Taylor J Schoen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-08T23:20:45Z |
| format | Article |
| id | doaj.art-54b4ec096f514a7f8c91391b1326d8c7 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-08T23:20:45Z |
| publishDate | 2023-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-54b4ec096f514a7f8c91391b1326d8c72023-12-15T05:31:43ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-05-01195e101115210.1371/journal.ppat.1011152Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection.Taylor J SchoenDante G CaliseJin Woo BokMorgan A GieseChibueze D NwagwuRobert ZarnowskiDavid AndesAnna HuttenlocherNancy P KellerHyphal 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.https://doi.org/10.1371/journal.ppat.1011152 |
| spellingShingle | Taylor J Schoen Dante G Calise Jin Woo Bok Morgan A Giese Chibueze D Nwagwu Robert Zarnowski David Andes Anna Huttenlocher Nancy P Keller Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection. PLoS Pathogens |
| 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 |
| url | https://doi.org/10.1371/journal.ppat.1011152 |
| work_keys_str_mv | AT taylorjschoen aspergillusfumigatustranscriptionfactorzfparegulateshyphaldevelopmentandalterssusceptibilitytoantifungalsandneutrophilkillingduringinfection AT dantegcalise aspergillusfumigatustranscriptionfactorzfparegulateshyphaldevelopmentandalterssusceptibilitytoantifungalsandneutrophilkillingduringinfection AT jinwoobok aspergillusfumigatustranscriptionfactorzfparegulateshyphaldevelopmentandalterssusceptibilitytoantifungalsandneutrophilkillingduringinfection AT morganagiese aspergillusfumigatustranscriptionfactorzfparegulateshyphaldevelopmentandalterssusceptibilitytoantifungalsandneutrophilkillingduringinfection AT chibuezednwagwu aspergillusfumigatustranscriptionfactorzfparegulateshyphaldevelopmentandalterssusceptibilitytoantifungalsandneutrophilkillingduringinfection AT robertzarnowski aspergillusfumigatustranscriptionfactorzfparegulateshyphaldevelopmentandalterssusceptibilitytoantifungalsandneutrophilkillingduringinfection AT davidandes aspergillusfumigatustranscriptionfactorzfparegulateshyphaldevelopmentandalterssusceptibilitytoantifungalsandneutrophilkillingduringinfection AT annahuttenlocher aspergillusfumigatustranscriptionfactorzfparegulateshyphaldevelopmentandalterssusceptibilitytoantifungalsandneutrophilkillingduringinfection AT nancypkeller aspergillusfumigatustranscriptionfactorzfparegulateshyphaldevelopmentandalterssusceptibilitytoantifungalsandneutrophilkillingduringinfection |