Estudo da atividade da GTPaseRas de Paracoccidioides brasiliensis durante o termo-dimorfismo do fungo e após estresse induzido por espécies reativas de oxigênio e nitrogênio

• Ano de defesa: 2017
• Autor(a) principal: Conceicao, Palloma Mendes [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/48912/0013000025mjq
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo
• Palavras-chave em Português: Paracoccidioides brasiliensis; Ras-MAPK pathway; Pathogenic fungi; Nitrosative and oxidative stress; Byr2 (STE11); Via Ras-MAPK; Fungos patogênicos; Estresse nitrosativo e oxidativo
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5636370; http://repositorio.unifesp.br/handle/11600/50499

Paracoccidioides brasiliensis, a thermally dependent dimorphic fungus, is one of the etiological agents of paracoccidioidomycosis (PCM). The ability to evade the innate immune response of the host and cause disease is particularly due to its ability to respond to and survive the nitrosative / oxidative stress caused by cells of the immune system. However, nothing is known about the regulation of signal transduction pathways associated with this resistance, possibly triggered by the reactive oxygen and nitrogen species generated by the host and that will act on this microorganism. Among the proteins that participate in cell signaling pathways, Ras is a GTPase with important role in different cellular processes, such as the control of morphological changes and cell proliferation. One of the main objectives of this work was to verify the activity of Ras under different study conditions. Initially it was observed that the fungus treated with Ras inhibitor and used to infect mice had a lower number of CFU in the lung when compared to the untreated control. These data suggest that Ras is important in fungal virulence. It has also been demonstrated that Ras is activated in response to oxidative, nitrosative and thermal stress. In addition, Ras-GTP participates in the transition from mycelial to yeast form. In this study it was also verified that Ras-GTP interacts with both Byr2 (Ste11) and Hog-1 in response to oxidative and nitrosative stress. Finally, it was verified that Ras can modulate the expression of some genes related to the response to oxidative and nitrosative stress. Therefore, this study presents a set of data indicating the presence of a (yet unknown) relationship between the Ras and Hog-1 signaling pathway in response to stress triggered by ROS / RNS, which may have been very important for the Response of P. brasiliensis to stress.