Aspergillus Fumigatus ZnfA, a Novel Zinc Finger Transcription Factor Involved in Calcium Metabolism and Caspofungin Tolerance

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Valero, Clara ; Colabardini, Ana Cristina ; de Castro, Patricia Alves ; Silva, Lilian Pereira ; Ries, Laure Nicolas Annick ; Pardeshi, Lakhansing ; Wang, Fang ; Rocha, Marina Campos ; Malavazi, Iran ; Silva, Roberto Nascimento ; Martins, Celso ; Domingos, Patricia ; Pereira-Silva, Cristina ; Bromley, Michael J. ; Wong, Koon Ho ; Goldman, Gustavo H.

• Document type: Journal article
• Source: FRONTIERS IN FUNGAL BIOLOGY; v. 2, p. 16-pg., 2021-08-10.

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. (AU)

• FAPESP's process: 16/21392-2 - "Characterization of transcription factors that have the basic domain" zipper "leucine (bZIP) ATF1 in Aspergillus fumigatus"
• Grantee: Lilian Pereira Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/07536-4 - Molecular Mechanisms Involved in Paradoxal Growth Induced by Caspofungin in Aspergillus fumigatus
• Grantee: Ana Cristina Colabardini
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/12948-7 - The role of mitogen-activated protein kinase (MPKA) MpkA in regulating gliotoxin production in Aspergillus fumigatus.
• Grantee: Patrícia Alves de Castro Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/07870-9 - The influence of mitogen activated protein kinases (MAPK) on the expression of genetic determinants important for Aspergillus fumigatus virulence
• Grantee: Gustavo Henrique Goldman
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/00315-5 - The influence of mitogen activated protein kinases (MAPK) on the expression of genetic determinants important for Aspergillus fumigatus virulence
• Grantee: Marina Campos Rocha
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/19694-3 - The role of heat shock proteins HsfA and Hsp90 and the regulator SmiA at cell wall integrity pathway activity in the opportunistic human pathogen Aspergillus fumigatus
• Grantee: Iran Malavazi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/00715-3 - Molecular characterization of Aspergillus fumigatus transcription factors involved in calcium metabolism.
• Grantee: Clara Isabel Valero Fernández
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/14159-2 - The role of lactose and acetate metabolism in Aspergillus fumigatus virulence
• Grantee: Laure Nicolas Annick Ries
• Support Opportunities: Research Grants - Young Investigators Grants