{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:29:05Z","timestamp":1768505345037,"version":"3.49.0"},"posted":{"date-parts":[[2023,1,26]]},"group-title":"Microbiology","reference-count":45,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,1,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Hyphal growth is essential for host colonization during\n                  <jats:italic>Aspergillus<\/jats:italic>\n                  infection. The transcription factor ZfpA regulates\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  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-\n                  <jats:italic>Aspergillus<\/jats:italic>\n                  infection model and primary human neutrophils to probe how ZfpA affects\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  pathogenesis and response to antifungal drugs\n                  <jats:italic>in vivo<\/jats:italic>\n                  . 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\n                  <jats:italic>ex vivo<\/jats:italic>\n                  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\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  infection.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Author Summary<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    is a common environmental fungus that can infect immunocompromised people and cause a life-threatening disease called invasive aspergillosis. An important step during infection is the development of\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    filaments known as hyphae.\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    uses hyphae to acquire nutrients and invade host tissues, leading to tissue damage and disseminated infection. In this study we report that a regulator of gene transcription in\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    called ZfpA is important for hyphal growth during infection. We find that ZfpA activity protects the fungus from being killed by innate immune cells and decreases the efficacy of antifungal drugs during infection by regulating construction of the cell wall, an important protective layer for fungal pathogens. Our study introduces ZfpA as an important genetic regulator of stress tolerance during infection that protects\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    from the host immune response and antifungal drugs.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.01.25.525624","type":"posted-content","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T20:35:15Z","timestamp":1674765315000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>Aspergillus fumigatus<\/i>\n                  transcription factor ZfpA regulates hyphal development and alters susceptibility to antifungals and neutrophil killing during infection"],"prefix":"10.64898","author":[{"given":"Taylor J.","family":"Schoen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dante G.","family":"Calise","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Woo","family":"Bok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chibueze D.","family":"Nwagwu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Zarnowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Andes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7940-6254","authenticated-orcid":false,"given":"Anna","family":"Huttenlocher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4386-9473","authenticated-orcid":false,"given":"Nancy P.","family":"Keller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023012718001731000_2023.01.25.525624v1.1","doi-asserted-by":"crossref","unstructured":"Latge JP , Chamilos G . 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