Study of the regulatory elements control the amino acids uptake in Cryptococcus neoformans

• Grant number: 18/20390-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2018
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Renata Castiglioni Pascon
• Grantee: Kevin Felipe Cruz Martho
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

The increasing incidence of invasive fungal infections caused by opportunistic fungi like Cryptococcus neoformans is in the fight against chronic diseases and immunodeficiency. The low repertoire of drugs and the treatment of resistance to antifungal drugs reflect the need for more potent and selective drugs. This aspect, the biosynthetic pathways and amino acid assimilation have been explored to obtain new molecular targets and have demonstrated high potential, since invasion by adaptation, adaptation and colonization of the host, are good targets for new forms of treatment. The genetic elements that regulate a biosynthesis and a capture of amino acids in a being unveiled by our group. This work was developed with the objective of investigating the data on the regulation of amino acid assimilation and its relation with survival and virulence. More specifically, the present work has three strands: (i) to test a possible cross-talk between the Ras1 pathway and amino acid uptake; (ii) to test a hypothesis that Zn-finger proteins CNAG_05392 and CNAG_03366 encode the Stp1 and Stp2 homologues, such as those known to trigger the activation of the amino acid uptake system in Saccharomyces cerevisiae (SPS-sensing); (iii) clarify the role of the transcription factor Cys3 and the Gpp2 phosphatase, which have recently been involved in the sulfur assimilation pathway and the biosynthesis of the sulfur amino acids. The two molecular and molecular techniques can be found in the work to better understand the mechanisms of activation, repression and interaction of proteins. This knowledge can lead to a higher rate of metabolism and virulence and thus propose new forms of treatment. (AU)

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)

DE MELO, AMANDA TEIXEIRA; MARTHO, KEVIN FELIPE; ROBERTO, THIAGO NUNES; NISHIDUKA, ERIKA S.; MACHADO JR, JOEL; BRUSTOLINI, OTAVIO J. B.; TASHIMA, ALEXANDRE K.; TEREZAVASCONCELOS, ANA; VALLIM, MARCELO A.; PASCON, RENATA C.. The regulation of the sulfur amino acid biosynthetic pathway in Cryptococcus neoformans: the relationship of Cys3, Calcineurin, and Gpp2 phosphatases. SCIENTIFIC REPORTS, v. 9, AUG 15 2019. (16/14542-8, 18/20390-1, 17/20106-9, 15/04400-9)

DA SILVA, JEYSON PEREIRA; MENEGHINI, MARIANA REIS; SANTOS, RONALDO SILVA; ALVES, VERONICA LIRA; MARTHO, KEVIN FELIPE DA CRUZ; VALLIM, MARCELO AFONSO; PASCON, RENATA CASTIGLIONI. ATP sulfurylase atypical leucine zipper interacts with Cys3 and calcineurin A in the regulation of sulfur amino acid biosynthesis in Cryptococcus neoformans. SCIENTIFIC REPORTS, v. 13, n. 1, p. 16-pg., 2023-07-20. (18/20390-1, 20/01000-8, 21/06290-7, 19/12051-5, 21/00725-1, 15/04400-9)