Characterization of phospho-mimetic mutants of kinases in Aspergillus fumigatus by CRISPR-cas 9 gene edition

• Grant number: 18/18043-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 01, 2018
• End date: September 30, 2019
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Gustavo Henrique Goldman
• Grantee: Eliciane Cevolani Mattos
• Supervisor: Uffe Hasbro Mortensen
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Technical University of Denmark (DTU), Denmark
• Associated to the scholarship: 17/19288-5 - Characterization of MAPKs dependent-phosphoproteomes of Aspergillus fumigatus under stress conditions, BP.PD

Abstract

Aspergillus fumigatus is an opportunistic and allergenic pathogenic fungus, responsible for about 65% of fungal infections in humans and for several pathologies in immunocompromised individuals, including invasive aspergillosis (IA). A. fumigatus has four MAPKs described: MpkA (central regulator of the CWI signaling pathway and acting in response to oxidative stress); MpkB (not well characterized); MpkC and SakA (orthologs of S. cerevisiae- Hog1, a kinase involved with the control of osmolarity glycerol response (HOG) pathway). Current studies are interested in the understand of the role of MAPKs in the cellular signaling triggered by treatment with stress-inductor molecules, as sorbitol or congo-red and caspofungin. It was recently demonstrated the involvement of Hog1 orthologous: SakA and MpkC, in the response to different cellular stresses as osmotic and oxidative stress, and in the fungus adaptation to caspofungin. In addition, MpkA has been related with the pathogen response to the caspofungin stress. The new gene edition strategies for the obtention of phosphomimetic mutants, as CRISPR-cas 9 for example, are important tools for the study of signaling pathways elements modulated by phosphorylation during a stress suffered by organisms. In this way, these BEPE project has as major aim to understand the cellular signaling mediated by phosphorylation of proteins involving the pathways of SakA and MpkC of A. fumigatus.

Scientific publications

(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)

MATTOS, ELICIANE CEVOLANI; SILVA, LILIAN PEREIRA; VALERO, CLARA; DE CASTRO, PATRICIA ALVES; DOS REIS, THAILA FERNANDA; RIBEIRO, LILIANE F. C.; MARTEN, MARK R.; SILVA-ROCHA, RAFAEL; WESTMANN, CAUA; TOMICH DE PAULA DA SILVA, CARLOS HENRIQUE; et al. The Aspergillus fumigatus Phosphoproteome Reveals Roles of High-Osmolarity Glycerol Mitogen-Activated Protein Kinases in Promoting Cell Wall Damage and Caspofungin Tolerance. MBIO, v. 11, n. 1, JAN-FEB 2020. (18/18043-1, 16/07870-9, 17/19288-5)