Molecular characterization of Aspergillus fumigatus transcription factors involved in calcium metabolism.

• Grant number: 18/00715-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2018
• End date: April 30, 2022
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Gustavo Henrique Goldman
• Grantee: Clara Isabel Valero Fernández
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 16/07870-9 - The influence of mitogen activated protein kinases (MAPK) on the expression of genetic determinants important for Aspergillus fumigatus virulence, AP.TEM
• Associated scholarship(s): 20/01131-5 - Identification of novel genes involved in stress response in Aspergillus fumigatus through quantitative barcode screening, BE.EP.PD

Abstract

Invasive aspergillosis (IA) is one of the most important human fungal infections, especially for immunocompromised population, with Aspergillus fumigatus being the most detected fungal species. When the fungus invades human lungs, it has to adapt to host environment in order to survive and to develop virulence strategies. In that context, the capacity of fungal cell wall to adapt to external stresses plays and important role. The study of those pathways resulting in maintaining cell wall robustness will help in the discovery of future antifungal drug targets, since they seem to be essential in fungal viability. Recently, six transcription factors (TFs) with different degrees of calcium (Ca2+) sensitivity has been identified, four of which are completely novel, suggesting that they could be involved in the signaling pathway in response to Ca2+ affecting osmotic or other stress responses. Our main aim is to characterize the role played by three of these novel TFs in Ca2+ metabolism. This will be addressed by following these main objectives: i) to characterize Ca2+- dependent TFs, both genetically and phenotypically; ii) to identificate of Ca2+-dependent TFs targets through RNAseq and ChIPseq methodologies; iii) to investigate the connections of Ca2+-dependent TFs with other signaling pathways and iv) to analyze the role of Ca2+- dependent TFs in virulence by using animal infection models and to characterize immune response in cell culture.

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VALERO, CLARA; COLABARDINI, ANA CRISTINA; DE CASTRO, PATRICIA ALVES; AMICH, JORGE; BROMLEY, MICHAEL J.; GOLDMAN, GUSTAVO H.. The Caspofungin Paradoxical Effect is a Tolerant "Eagle Effect" in the Filamentous Fungal Pathogen Aspergillus fumigatus. MBIO, v. N/A, p. 6-pg., 2022-04-14. (16/12948-7, 16/07870-9, 18/00715-3, 17/07536-4)

STEENWYK, JACOB L.; MEAD, MATTHEW E.; DE CASTRO, PATRICIA ALVES; VALERO, CLARA; DAMASIO, ANDRE; DOS SANTOS, RENATO A. C.; LABELLA, ABIGAIL L.; LI, YUANNING; KNOWLES, SONJA L.; RAJA, HUZEFA A.; et al. Genomic and Phenotypic Analysis of COVID-19-Associated Pulmonary Aspergillosis Isolates of Aspergillus fumigatus. MICROBIOLOGY SPECTRUM, v. 9, n. 1, SEP 2021. (19/07526-4, 17/21983-3, 18/00715-3)

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; et al. Aspergillus Fumigatus ZnfA, a Novel Zinc Finger Transcription Factor Involved in Calcium Metabolism and Caspofungin Tolerance. FRONTIERS IN FUNGAL BIOLOGY, v. 2, p. 16-pg., 2021-08-10. (16/21392-2, 17/07536-4, 16/12948-7, 16/07870-9, 18/00315-5, 17/19694-3, 18/00715-3, 17/14159-2)

DA COSTA FILHO, AILTON PEREIRA; PEREIRA BRANCINI, GUILHERME THOMAZ; DE CASTRO, PATRICIA ALVES; VALERO, CLARA; FERREIRA FILHO, JAIRE ALVES; SILVA, LILIAN PEREIRA; ROCHA, MARINA CAMPOS; MALAVAZI, IRAN; DE MORAES PONTES, JOAO GUILHERME; FILL, TAICIA; et al. Aspergillus fumigatus G-Protein Coupled Receptors GprM and GprJ Are Important for the Regulation of the Cell Wall Integrity Pathway, Secondary Metabolite Production, and Virulence. MBIO, v. 11, n. 5, SEP-OCT 2020. (16/07870-9, 18/10962-8, 18/25217-6, 19/11929-7, 17/14159-2, 16/12948-7, 18/00715-3, 19/10727-1, 19/06359-7, 16/21392-2)

COLABARDINI, ANA CRISTINA; VAN RHIJN, NORMAN; LABELLA, ABIGAIL L.; VALERO, CLARA; DINEEN, LAUREN; ROKAS, ANTONIS; GOLDMAN, GUSTAVO H.. Aspergillus fumigatus FhdA Transcription Factor Is Important for Mitochondrial Activity and Codon Usage Regulation during the Caspofungin Paradoxical Effect. Antimicrobial Agents and Chemotherapy, v. 66, n. 9, p. 4-pg., 2022-08-02. (18/00715-3, 17/07536-4, 16/07870-9)

ANNICK RIES, LAURE NICOLAS; DE CASTRO, PATRICIA ALVES; SILVA, LILIAN PEREIRA; VALERO, CLARA; DOS REIS, THAILA FERNANDA; SABORANO, RAQUEL; DUARTE, IOLA F.; PERSINOTI, GABRIELA FELIX; STEENWYK, JACOB L.; ROKAS, ANTONIS; et al. spergillus fumigatus Acetate Utilization Impacts Virulence Traits and Pathogenicit. MBIO, v. 12, n. 4, JUL-AUG 2021. (16/07870-9, 17/14159-2, 17/08750-0, 16/12948-7, 18/00715-3)

DE CASTRO, PATRICIA ALVES; VALERO, CLARA; CHIARATTO, JESSICA; COLABARDINI, ANA CRISTINA; PARDESHI, LAKHANSING; SILVA, LILIAN PEREIRA; ALMEIDA, FAUSTO; ROCHA, MARINA CAMPOS; SILVA, ROBERTO NASCIMENTO; MALAVAZI, IRAN; et al. Novel Biological Functions of the NsdC Transcription Factor in Aspergillus fumigatus. MBIO, v. 12, n. 1, JAN-FEB 2021. (16/07870-9, 18/00715-3, 16/21392-2, 17/07536-4, 16/22062-6, 16/12948-7, 19/10097-8)

VALERO, CLARA; COLABARDINI, ANA CRISTINA; CHIARATTO, JESSICA; PARDESHI, LAKHANSING; DE CASTRO, PATRICIA ALVES; FERREIRA FILHO, JAIRE ALVES; SILVA, LILIAN PEREIRA; ROCHA, MARINA CAMPOS; MALAVAZI, IRAN; COSTA, JONAS HENRIQUE; et al. Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect. MBIO, v. 11, n. 3, p. 22-pg., 2020-05-01. (16/21392-2, 17/07536-4, 16/12948-7, 16/07870-9, 16/22062-6, 18/00715-3)