Evaluation of S-nitrosylated proteins of the Paracoccidioides brasiliensis after nitrosative stress and identification of potential redox signaling pathways

• Grant number: 17/04592-0
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2017
• End date: October 31, 2019
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Wagner Luiz Batista
• Grantee: Wagner Luiz Batista
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated researchers: Patricia Xander Batista

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 is 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 occur 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

(8)

(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)

ELLER-BORGES, ROBERTA; RODRIGUES, ELAINE G.; TEODORO, ANA CAROLINE S.; MORAES, MIRIAM S.; ARRUDA, DENISE C.; PASCHOALIN, THAYSA; CURCIO, MARLI F.; COSTA, PAULO E. DA; NASCIMENTO, IGOR R. DO; CALIXTO, LEANDRO A.; et al. Bradykinin promotes murine melanoma cell migration and invasion through endogenous production of superoxide and nitric oxide. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 132, p. 12-pg., 2023-02-03. (17/04592-0, 18/15038-7, 12/10470-1)

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)

CASTILHO, DANIELE GONCALVES; ALENCAR CHAVES, ALISON FELIPE; NAVARRO, MARINA VALENTE; CONCEICAO, PALLOMA MENDES; FERREIRA, KAREN SPADARI; DA SILVA, LUIZ SEVERINO; XANDER, PATRICIA; BATISTA, WAGNER LUIZ. Secreted aspartyl proteinase (PbSap) contributes to the virulence of Paracoccidioides brasiliensis infection. PLoS Neglected Tropical Diseases, v. 12, n. 9, SEP 2018. (17/04592-0, 14/13961-1, 14/08987-1)

CHAVES, ALISON FELIPE ALENCAR; XANDER, PATRICIA; ROMERA, LAVINIA MARIA DAL'MAS; FONSECA, FERNANDO LUIZ AFFONSO; BATISTA, WAGNER LUIZ. What is the elephant in the room when considering new therapies for fungal diseases?. CRITICAL REVIEWS IN MICROBIOLOGY, v. 47, n. 3, JAN 2021. (15/09727-6, 17/04592-0)

CONCEICAO, PALLOMA MENDES; ALENCAR CHAVES, ALISON FELIPE; NAVARRO, MARINA VALENTE; CASTILHO, DANIELE GONCALVES; CALADO, JULIANA CRISTINA P.; CORONEL JANU HANIU, ANA ELIZA; XANDER, PATRICIA; BATISTA, WAGNER L.. Cross-talk between the Ras GTPase and the Hog1 survival pathways in response to nitrosative stress in Paracoccidioides brasiliensis. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 86, p. 1-11, MAY 1 2019. (17/04592-0)

CASTILHO, DANIELE G.; NAVARRO, MARINA V.; CHAVES, ALISON F. A.; XANDER, PATRICIA; BATISTA, WAGNER L.. Recovery of the Paracoccidioides brasiliensis virulence after animal passage promotes changes in the antioxidant repertoire of the fungus. FEMS Yeast Research, v. 18, n. 2, MAR 2018. (14/13961-1, 17/04592-0, 14/08987-1)

ALENCAR CHAVES, ALISON FELIPE; NAVARRO, MARINA VALENTE; DE BARROS, YASMIN NASCIMENTO; SILVA, RAFAEL SOUZA; XANDER, PATRICIA; BATISTA, WAGNER LUIZ. Updates in Paracoccidioides Biology and Genetic Advances in Fungus Manipulation. JOURNAL OF FUNGI, v. 7, n. 2, FEB 2021. (17/04592-0)

SILVA, RAFAEL DE SOUZA; SEGURA, WILSON DIAS; OLIVEIRA, REINALDO SOUZA; XANDER, PATRICIA; BATISTA, WAGNER LUIZ. Characterization of Aspartic Proteases from Paracoccidioides brasiliensis and Their Role in Fungal Thermo-Dimorphism. JOURNAL OF FUNGI, v. 9, n. 3, p. 19-pg., 2023-03-01. (17/04592-0, 20/14235-3)