Molecular characterization of a receptor coupled to a G protein (GPCR) of Aspergillus fumigatus

Author(s)

Ailton Pereira da Costa Filho

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2021-06-23

Examining board members

Gustavo Henrique Goldman; Leonardo Nimrichter; Livia Kmetzsch Rosa e Silva

• Advisor: Gustavo Henrique Goldman; Thaila Fernanda dos Reis

Abstract

Aspergillus fumigatus is an opportunistic fungus with potential lethality. Due to the small size of its conidia, the lungs are easily reached. In propitious temperature, the fungus germinates and can cause damage to the host. Immunocompromised individuals are potential hosts because the immune system is unable to eliminate conidia in early stages of infection and consequently become victims of aspergillosis. Through signal transduction pathways, opportunistic fungi like A. fumigatus perceive the environment, modulate their metabolism in order to evade the host\'s immune system. GPCRs are examples of signal transducers pathways with at least 15 putative GPCRs identified in A. fumigatus, which have already been identified as likely pheromone and cAMP receptors and carbon and nitrogen sensors. Recently, our laboratory characterized GprM and GprJ as important modulators of melanin production and the Cell Wall Integrity Pathway, in addition to the protein kinase MpkA. The sugar content in the cell walls was variable between the mutants and the wild-type strain, moreover the transcriptome showed that gprM and gprJ negatively regulate genes responsible for the production of secondary metabolites: fumagillin, pyripyropene, fumigaclavin C, fumiquinazoline and fumitremorgin. It was also observed that the overexpression of gprM modulates the transcription factor asgA, which was shown to be downstream of gprM and MpkA signaling. The ΔgprM and ΔgprJ mutants have shown reduced virulence in Galleria mellonella larvae, which consists as a study model for invasive aspergillosis. Therefore, the characterization of genes and related pathways in A. fumigatus provides knowledge of virulence mechanisms and can benefit immunocompromised individuals. (AU)

• FAPESP's process: 19/10727-1 - Molecular characterization of a receptor coupled to a g protein (GPCR) of Aspergillus fumigatus
• Grantee: Ailton Pereira da Costa Filho
• Support Opportunities: Scholarships in Brazil - Master