Global analysis of S-nitrosylation sites in proteins of Paracoccidioides brasiliensis after nitrosative stress

• Grant number: 15/09654-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2015
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Wagner Luiz Batista
• Grantee: Marina Valente Navarro
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This fungus is considered a facultative intracellular pathogen, able to survive and replicate inside macrophages. The survival of P. brasiliensis in the host depends on the fungus adaptation in several conditions, such as oxidative and nitrosative stress produced by host immune cells, particularly alveolar macrophages. Currently, there are few knowledge about the P. brasiliensis signaling pathways involved in the fungus evasion mechanisms of the host defense response. However, it is know that some of these pathways are triggered by reactive oxygen and nitrogen species (ROS/RNS) produced by host cells. These regulation events are dynamic and may influence (activating or inhibiting) several protein functions. Among various oxidative reactions that occurs in cysteine residues, S-nitrosylation stands out as an important nitric oxide (NO) dependent post-translational modification, which regulates a variety of cellular functions and signaling events. Recently our group demonstrated that P. brasiliensis yeast cells proliferate when exposed to low concentrations of nitric oxide. Thus, this work proposes to evaluate the S-nitrosylated protein profile, as well as the identification of S-nitrosylation sites after exposure to different concentrations of RNS. The identification of S-nitrosylated proteins after low concentrations of NO, which has lead to cell proliferation in our model, can represent molecules involved in fungus virulence. Moreover, the analysis of S-nitrosylated proteins after high concentrations of NO may assist the understanding of RNS antifungal properties and identify potential molecular target to further development of new drugs. (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)

NAVARRO, MARINA V.; CHAVES, ALISON F. A.; CASTILHO, DANIELE G.; CASULA, ISIS; CALADO, JULIANA C. P.; CONCEICAO, PALLOMA M.; IWAI, LEO K.; DE CASTRO, BEATRIZ F.; BATISTA, WAGNER L.. Effect of Nitrosative Stress on theS-Nitroso-Proteome ofParacoccidioides brasiliensis. FRONTIERS IN MICROBIOLOGY, v. 11, JUN 4 2020. (17/04592-0, 13/07467-1, 16/04000-3, 15/09654-9, 17/17943-6)