PLOS Pathogens · 15 authors, 9 centres
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Using a zebrafish infection model and human neutrophils, this preclinical study found that deleting the fungal transcription factor ZfpA makes Aspergillus fumigatus more susceptible to immune clearance and antifungal drugs, while overexpression protects the fungus, suggesting ZfpA is a key regulator of pathogen defense during infection.
This preclinical study used larval zebrafish and primary human neutrophils to investigate the role of the Aspergillus fumigatus transcription factor ZfpA during infection. The researchers found that ZfpA deletion attenuated virulence and decreased fungal burden in immunocompetent zebrafish, but this defect was absent in neutrophil-deficient hosts. In ex vivo assays, ZfpA deletion increased hyphal susceptibility to neutrophil killing, while overexpression conferred protection. Mechanistically, ZfpA overexpression increased chitin synthesis and conferred resistance to the antifungal caspofungin, whereas deletion reduced chitin and increased susceptibility. The study demonstrates ZfpA is a protective regulator of hyphal stress tolerance against both the innate immune response and antifungal treatment. Limitations include the use of a zebrafish model and indirect human relevance via ex vivo neutrophil assays, and the need for more comprehensive cell wall composition analysis.
