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Calcineurin and cAMP/PKA on phisiology and stress in the fungus Paracoccidioides brasiliensis


The Paracoccidioides brasiliensis, the etiological agent of paracoccidioidomycosis in Brazil, Colombia and Venezuela, alternate their morphology due to temperature variations (thermodimorphism), and the transition from a non-infective (mycelium) to infective (yeast) is essential for the establishment of the disease. In fungi, in concert to the process of dimorphism, undergo other adaptive changes that enable them to survive and proliferate in the human host. There are several cell signaling pathways that can control the morphology and other aspects of fungal physiology in response to environmental stimuli, and the phosphatase calcineurin is frequently related to control differentiation and proliferation processes, as well as the ability to cause disease. Our group showed evidence that calcineurin controls these processes in also P. brasiliensis (Campos et al, 2008). This project aims to extend the analysis of the role of calcineurin in biology and physiology of P. brasiliensis, specifically on the dimorphism, proliferation and mitochondrial function, and to identify signaling pathways with which calcineurin interacts. The pathway of choice is the cAMP / PKA pathway, described counteract the effect of calcineurin in fungal models and other biological systems. Initially, we will use compounds that modulate the generation of cAMP and PKA activity and subsequently tested their effects over those observed when cyclosporine A is used. It is proposed also to assess whether and how PKA and calcineurin act on mitochondrial function under different experimental conditions. This study aims to expand knowledge about the molecular mechanisms involved in morphological transition and the development of pathogenicity and virulence of P. brasiliensis. We believe that behind the mechanisms controlled by calcineurin and cAMP / PKA may be a promising target for future therapeutic intervention or for prophylaxis against this and probably other pathogenic fungi. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MATOS, TATIANA G. F.; MORAIS, FLAVIA V.; CAMPOS, CLAUDIA B. L.. Hsp90 regulates Paracoccidioides brasiliensis proliferation and ROS levels under thermal stress and cooperates with calcineurin to control yeast to mycelium dimorphism. Medical Mycology, v. 51, n. 4, p. 413-421, . (10/50078-8)

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