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Molecular characterization of Aspergillus fumigatus GprJ, a G protein-coupled receptor involved in the control of melanin production

Grant number: 19/11929-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2019
Effective date (End): November 30, 2020
Field of knowledge:Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
Principal researcher:Gustavo Henrique Goldman
Grantee:Guilherme Thomaz Pereira Brancini
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Aspergillus fumigatus is the most ubiquitous of fungi with airborne spores and inhaling of such structures can lead to Chronic Pulmonary Aspergillosis in immunocompromised individuals. The disease is a serious one and mortality can reach 100% if diagnosis is delayed. Essential to A. fumigatus survival both in decaying matter and in host tissues is the ability to sense the environment. G Protein-Coupled Receptors (GPCRs) are seven transmembrane domain proteins that are involved in response to external stimuli such as hormones, nutrients, protein, ions, and light. Upon activation, GPCRs change their conformation and trigger the dissociation between G± and the heterodimer G²³, each of which will act to activate or inhibit downstream signaling pathways. Because they are very important to cell signaling and are easily accessible at the cell surface, GPCRs are commonly used as drug targets. Indeed, an estimated 34% of all approved drugs target a GPCR. However, knowledge about fungal GPCRs is scarce, especially so for filamentous fungi. Only three of the 15 predicted A. fumigatus GPCRs have been characterized to date. Studying GPCRs can be difficult because the majority of gene deletion strains show no obvious phenotype. A previous screening of a library containing deletion mutants for all 15 predicted GPCRs revealed that the “gprJ strain produces a dark pigment when grown in liquid medium, thus indicating that it could regulate melanin production. The present research project proposes to characterize GprJ, including its role in growth, tolerance to different stressors, virulence, MAP Kinase signaling, global gene expression, and interacting partners. Our results will help in understanding how A. fumigatus senses its environment and will produce important knowledge about fungal GPCRs. (AU)

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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)
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; SILVA, ROBERTO NASCIMENTO; ALMEIDA, FAUSTO; STEENWYK, JACOB L.; ROKAS, ANTONIS; DOS REIS, THAILA F.; RIES, LAURE N. A.; GOLDMAN, GUSTAVO H. 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. Web of Science Citations: 1.

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