| Grant number: | 11/14392-2 |
| Support Opportunities: | Regular Research Grants |
| Start date: | October 01, 2011 |
| End date: | September 30, 2013 |
| 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: | Alexandre Keiji Tashima ; Hugo Pequeno Monteiro ; Juliana Terzi Maricato ; Patricia Xander Batista |
Abstract
Paracoccidioides brasiliensis, a thermo-dimorphic fungus, is the etiologic agent of the most prevalent systemic mycosis in Latin America, paracoccidioidomycosis (PCM). The infection occurs by inhalation of conidia present in the environment. The development of the disease depends on the change of conidia to yeast form, an event caused by temperature increasing. The fungus acts as optional intracellular pathogen able to survive and replicate in non-activated macrophages. This ability to escape the host innate immune response and thus cause the disease is particularly due to its ability to react and survive to nitrosative and oxidative stress caused by immune cells, especially alveolar macrophages. However, the regulation of signal transduction pathways associated with this resistance is poorly known. Among the proteins that participate in cell signaling pathways stands Ras, a GTPase with an important role in various cellular processes such as control of morphological changes, cell proliferation and stress response. In P. brasiliensis were identified two isoforms of this protein, ras1 and ras2, which are homologous to other fungi. Currently there are experimental evidence of the involvement of free radicals and other reactive species in signal transduction pathways. In redox condition, Ras can undergo post-translational modifications with reversible nature (S-nitrosylation) which can activate and modulate this molecule. Thus, this project proposes to evaluate the process of activating the Ras protein of P. brasiliensis, after exposure of the fungus to different concentrations of ROS and/or RNS. The development of this project will certainly lead to understanding of parasite-host relationship from a different perspective in this and in other mycoses. (AU)
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