AUTHOR=Valero Clara , Colabardini Ana Cristina , de Castro Patrícia Alves , Silva Lilian Pereira , Ries Laure Nicolas Annick , Pardeshi Lakhansing , Wang Fang , Rocha Marina Campos , Malavazi Iran , Silva Roberto Nascimento , Martins Celso , Domingos Patrícia , Pereira-Silva Cristina , Bromley Michael J. , Wong Koon Ho , Goldman Gustavo H. TITLE=Aspergillus Fumigatus ZnfA, a Novel Zinc Finger Transcription Factor Involved in Calcium Metabolism and Caspofungin Tolerance JOURNAL=Frontiers in Fungal Biology VOLUME=2 YEAR=2021 URL=https://www.frontiersin.org/journals/fungal-biology/articles/10.3389/ffunb.2021.689900 DOI=10.3389/ffunb.2021.689900 ISSN=2673-6128 ABSTRACT=

Invasive pulmonary aspergillosis is a life-threatening fungal infection especially in the immunocompromised patients. The low diversity of available antifungal drugs coupled with the emergence of antifungal resistance has become a worldwide clinical concern. The echinocandin Caspofungin (CSP) is recommended as a second-line therapy but resistance and tolerance mechanisms have been reported. However, how the fungal cell articulates the response to CSP is not completely understood. This work provides a detailed characterization of ZnfA, a transcription factor (TF) identified in previous screening studies that is involved in the A. fumigatus responses to calcium and CSP. This TF plays an important role in the regulation of iron homeostasis and cell wall organization in response to high CSP concentrations as revealed by Chromatin Immunoprecipitation coupled to DNA sequencing (ChIP-seq) analysis. Furthermore, ZnfA acts collaboratively with the key TF CrzA in modulating the response to calcium as well as cell wall and osmotic stresses. This study therefore describes the existence of an additional, previously unknown TF that bridges calcium signaling and the CSP cellular response and further exposes the complex connections that exist among different pathways which govern stress sensing and signaling in A. fumigatus.