Cross-talk between the Ras GTPase and the Hog1 survival pathways in response to nitrosative stress in Paracoccidioides brasiliensis

Autor(es)

Conceicao, Palloma Mendes ^[1] ; Alencar Chaves, Alison Felipe ^[2] ; Navarro, Marina Valente ^[2] ; Castilho, Daniele Goncalves ^[2] ; Calado, Juliana Cristina P. ^[2] ; Coronel Janu Haniu, Ana Eliza ^[2] ; Xander, Patricia ^[1] ; Batista, Wagner L. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Campus Diadema, Diadema, SP - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Diadema, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 86, p. 1-11, MAY 1 2019.
• Citações Web of Science: 0

Resumo

Paracoccidioides brasiliensis is a temperature-dependent dimorphic fungus that cause paracoccidioidomycosis (PCM), the major systemic mycosis in Latin America. The capacity to evade the innate immune response of the host is due to P. brasiliensis ability to respond and to survive the nitrosative stress caused by phagocytic cells. However, the regulation of signal transduction pathways associated to nitrosative stress response are poorly understood. Ras GTPase play an important role in the various cellular events in many fungi. Ras, in its activated form (Ras-GTP), interacts with effector proteins and can initiate a kinase cascade. In this report, we investigated the role of Ras GTPase in P. brasiliensis after in vitro stimulus with nitric oxide (NO). We observed that low concentrations of NO induced cell proliferation in P. brasiliensis, while high concentrations promoted decrease in fungal viability, and both events were reversed in the presence of a NO scavenger. We observed that high levels of NO induced Ras activation and its S-nitrosylation. Additionally, we showed that Ras modulated the expression of antioxidant genes in response to nitrosative stress. We find that the Hog1 MAP kinase contributed to nitrosative stress response in P. brasiliensis in a Ras-dependent manner. Taken together, our data demonstrate the relationship between Ras-GTPase and Hog1 MAPK pathway allowing for the P. brasiliensis adaptation to nitrosative stress. (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