PUBLICATION
Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection
- Authors
- Schoen, T.J., Calise, D.G., Bok, J.W., Giese, M.A., Nwagwu, C.D., Zarnowski, R., Andes, D., Huttenlocher, A., Keller, N.P.
- ID
- ZDB-PUB-230502-39
- Date
- 2023
- Source
- PLoS pathogens 19: e1011152e1011152 (Journal)
- Registered Authors
- Huttenlocher, Anna
- Keywords
- none
- MeSH Terms
-
- Animals
- Antifungal Agents/pharmacology
- Aspergillosis*/microbiology
- Aspergillus fumigatus*
- Caspofungin/pharmacology
- Chitin
- Fungal Proteins/genetics
- Fungal Proteins/metabolism
- Gene Expression Regulation, Fungal
- Humans
- Neutrophils
- Transcription Factors/metabolism
- Zebrafish/metabolism
- PubMed
- 37126504 Full text @ PLoS Pathog.
Citation
Schoen, T.J., Calise, D.G., Bok, J.W., Giese, M.A., Nwagwu, C.D., Zarnowski, R., Andes, D., Huttenlocher, A., Keller, N.P. (2023) Aspergillus fumigatus transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection. PLoS pathogens. 19:e1011152e1011152.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping