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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Effect of Nitrosative Stress on theS-Nitroso-Proteome ofParacoccidioides brasiliensis

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Autor(es):
Navarro, Marina V. [1] ; Chaves, Alison F. A. [1] ; Castilho, Daniele G. [1] ; Casula, Isis [2] ; Calado, Juliana C. P. [1] ; Conceicao, Palloma M. [2] ; Iwai, Leo K. [3] ; de Castro, Beatriz F. [2] ; Batista, Wagner L. [1, 2]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Escola Paulista Med, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Inst Ciencias Ambientais Quim & Farmaceut, Diadema - Brazil
[3] Inst Butantan, Lab Appl Toxinol, Ctr Toxins Immune Response & Cell Signaling, Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN MICROBIOLOGY; v. 11, JUN 4 2020.
Citações Web of Science: 0
Resumo

The fungiParacoccidioides brasiliensisandParacoccidioides lutziiare the causative agents of paracoccidioidomycosis (PCM), a systemic mycosis endemic to Latin America. This fungus is considered a facultative intracellular pathogen that is able to survive and replicate inside macrophages. The survival of the fungus during infection depends on its adaptability to various conditions, such as nitrosative/oxidative stress produced by the host immune cells, particularly alveolar macrophages. Currently, there is little knowledge about theParacoccidioidesspp. signaling pathways involved in the fungus evasion mechanism of the host defense response. However, it is known that some of these pathways are triggered by reactive oxygen species and reactive nitrogen species (ROS/RNS) produced by host cells. Considering that the effects of NO (nitric oxide) on pathogens are concentration dependent, such effects could alter the redox state of cysteine residues by influencing (activating or inhibiting) a variety of protein functions, notablyS-nitrosylation, a highly important NO-dependent posttranslational modification that regulates cellular functions and signaling pathways. It has been demonstrated by our group thatP. brasiliensisyeast cells proliferate when exposed to low NO concentrations. Thus, this work investigated the modulation profile ofS-nitrosylated proteins ofP. brasiliensis, as well as identifyingS-nitrosylation sites after treatment with RNS. Through mass spectrometry analysis (LC-MS/MS) and label-free quantification, it was possible to identify 474 proteins in theS-nitrosylated proteome study. With this approach, we observed that proteins treated with NO at low concentrations presented a proliferative response pattern, with several proteins involved in cellular cycle regulation and growth being activated. These proteins appear to play important roles in fungal virulence. On the other hand, fungus stimulated by high NO concentrations exhibited a survival response pattern. Among theseS-nitrosylated proteins we identified several potential molecular targets for fungal disease therapy, including cell wall integrity (CWI) pathway, amino acid and folic acid metabolisms. In addition, we detected that the transnitrosylation/denitrosylation redox signaling are preserved in this fungus. Finally, this work may help to uncover the beneficial and antifungal properties of NO in theP. brasiliensisand point to useful targets for the development of antifungal drugs. (AU)

Processo FAPESP: 17/04592-0 - Avaliação das proteínas S-nitrosiladas do fungo Paracoccidioides brasiliensis após estresse nitrosativo e identificação de potenciais vias de sinalização redox
Beneficiário:Wagner Luiz Batista
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
Beneficiário:Hugo Aguirre Armelin
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 16/04000-3 - Farmacologia de oligopeptidases e peptídeos intracelulares
Beneficiário:Emer Suavinho Ferro
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 15/09654-9 - Avaliação de modificações pós-traducionais de caráter redox do fungo Paracoccidioides brasiliensis após estresse nitrosativo
Beneficiário:Marina Valente Navarro
Modalidade de apoio: Bolsas no Brasil - Mestrado
Processo FAPESP: 17/17943-6 - Análise proteômica e peptidômica do efeito da peçonha de serpentes sobre linhagens celulares de câncer e tecidos cerebrais de camundongos
Beneficiário:Leo Kei Iwai
Modalidade de apoio: Auxílio à Pesquisa - Regular