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Evaluation of the involvement of Ras GTPase from Paracoccidioides brasiliensis in thermo-dimorphism and during oxidative and nitrosative stress

Grant number: 11/14392-2
Support type:Regular Research Grants
Duration: October 01, 2011 - September 30, 2013
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Wagner Luiz Batista
Grantee:Wagner Luiz Batista
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
Assoc. researchers:Alexandre Keiji Tashima ; Hugo Pequeno Monteiro ; Juliana Terzi Maricato ; Patricia Xander Batista

Abstract

Paracoccidioides brasiliensis, a thermo-dimorphic fungus, is the etiologic agent of the most prevalent systemic mycosis in Latin America, paracoccidioidomycosis (PCM). The infection occurs by inhalation of conidia present in the environment. The development of the disease depends on the change of conidia to yeast form, an event caused by temperature increasing. The fungus acts as optional intracellular pathogen able to survive and replicate in non-activated macrophages. This ability to escape the host innate immune response and thus cause the disease is particularly due to its ability to react and survive to nitrosative and oxidative stress caused by immune cells, especially alveolar macrophages. However, the regulation of signal transduction pathways associated with this resistance is poorly known. Among the proteins that participate in cell signaling pathways stands Ras, a GTPase with an important role in various cellular processes such as control of morphological changes, cell proliferation and stress response. In P. brasiliensis were identified two isoforms of this protein, ras1 and ras2, which are homologous to other fungi. Currently there are experimental evidence of the involvement of free radicals and other reactive species in signal transduction pathways. In redox condition, Ras can undergo post-translational modifications with reversible nature (S-nitrosylation) which can activate and modulate this molecule. Thus, this project proposes to evaluate the process of activating the Ras protein of P. brasiliensis, after exposure of the fungus to different concentrations of ROS and/or RNS. The development of this project will certainly lead to understanding of parasite-host relationship from a different perspective in this and in other mycoses. (AU)

Scientific publications (6)
(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)
CHAVES, ALISON F. A.; CASTILHO, DANIELE G.; NAVARRO, MARINA V.; OLIVEIRA, ANA K.; SERRANO, SOLANGE M. T.; TASHIMA, ALEXANDRE K.; BATISTA, WAGNER L. Phosphosite-specific regulation of the oxidative-stress response of Paracoccidioides brasiliensis: a shotgun phosphoproteomic analysis. Microbes and Infection, v. 19, n. 1, p. 34-46, JAN 2017. Web of Science Citations: 3.
TASHIMA, ALEXANDRE KEIJI; CASTILHO, DANIELE GONCALVES; ALENCAR CHAVES, ALISON FELIPE; XANDER, PATRICIA; ZELANIS, ANDRE; BATISTA, WAGNER LUIZ. Data in support of quantitative proteomics to identify potential virulence regulators in Paracoccidioides brasiliensis isolates. DATA IN BRIEF, v. 5, p. 155-160, DEC 2015. Web of Science Citations: 0.
ELLER-BORGES, ROBERTA; BATISTA, WAGNER L.; DA COSTA, PAULO E.; TOKIKAWA, RITA; CURCIO, MARLI F.; STRUMILLO, SCHEILLA T.; SARTORI, ADRIANO; MORAES, MIRIAM S.; DE OLIVEIRA, GRACIELE A.; TAHA, MURCHED O.; FONSECA, FABIO V.; STERN, ARNOLD; MONTEIRO, HUGO P. Ras, Rac1, and phosphatidylinositol-3-kinase (PI3K) signaling in nitric oxide induced endothelial cell migration. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 47, p. 40-51, MAY 1 2015. Web of Science Citations: 11.
CASTILHO, DANIELE G.; CHAVES, ALISON F. A.; XANDER, PATRICIA; ZELANIS, ANDRE; KITANO, EDUARDO S.; SERRANO, SOLANGE M. T.; TASHIMA, ALEXANDRE K.; BATISTA, WAGNER L. Exploring Potential Virulence Regulators in Paracoccidioides brasiliensis Isolates of Varying Virulence through Quantitative Proteomics. JOURNAL OF PROTEOME RESEARCH, v. 13, n. 10, p. 4259-4271, 2014. Web of Science Citations: 8.
CORONEL JANU HANIU, ANA ELIZA; MARICATO, JULIANA TERZI; MORAES MATHIAS, PEDRO PAULO; CASTILHO, DANIELE GONCALVES; MIGUEL, RODRIGO BERNARDI; MONTEIRO, HUGO PEQUENO; PUCCIA, ROSANA; BATISTA, WAGNER LUIZ. Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner. PLoS One, v. 8, n. 7 JUL 29 2013. Web of Science Citations: 11.
BATISTA, WAGNER L.; OGATA, FERNANDO T.; CURCIO, MARLI F.; MIGUEL, RODRIGO B.; ARAI, ROBERTO J.; MATSUO, ALISSON L.; MORAES, MIRIAM S.; STERN, ARNOLD; MONTEIRO, HUGO P. S-Nitrosoglutathione and Endothelial Nitric Oxide Synthase-Derived Nitric Oxide Regulate Compartmentalized Ras S-Nitrosylation and Stimulate Cell Proliferation. Antioxidants & Redox Signaling, v. 18, n. 3, p. 221-238, JAN 2013. Web of Science Citations: 26.

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