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Study of autophagy in Paracoccidioides genus: importance in fungal dimorphism and adaptation

Abstract

Autophagy is a cellular mechanism highly conserved in eukaryotic organisms. This process allows the degradation by cells, in large scale, of macromolecules and organelles. Currently, scientific studies demonstrate the importance of autophagy in several biological cellular processes such as in adaptation, differentiation and cellular development. Autophagy has been well described controlling homeostasis, allowing cellular adaptation to specific nutrients and/or organism survival against different types of stresses. The Paracoccidioides brasiliensis is the thermodimorphic fungus responsible for pacoccidioidomicosis in humans. P. brasiliensis infection occurs through conidia inhalation, but the disease is only established after morphological transition from mycelia (infective form) to yeast (parasitic form) inside the host. The factors involved in this transition are not yet completely described, although it is known that increase in temperature is essential. Because dimorphism of P. brasiliensis is triggered by a thermic stress, that is the temperature shift from 25 °C to 36 °C, the objective of this project is to evaluate if autophagy has a relevant role during this cellular event. Moreover, the present project aims to verify the existence of a relationship between the autophagy process and the different behavior of the three P. brasiliensis isolates in which virulence and pathogenicity have been described in experimental models. In this project, the prototype isolates of P. brasiliensis Pb18 and Pb03, and the isolate Pb01 (recently classified as other specie, Paracoccidiodes lutzii, by Teixeira el al., 2009), of which genomes had been sequenced and "in vitro" pathogenicity has been well established, will be used. The autophagic process of these isolates will be verified during dimorphism and under nutritional starvation by coloring autophagic vacuoles, observation of hyphal tips alterations and gene expression, in presence or not of drugs that modulate autophagy. (AU)

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VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)