XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:110-1

Poster (Painel)

110-1	Hsp-90 cooperate with calcineurin to promote mycelium to yeast transition in Paracoccidioides brasiliensis
Authors:	Tatiana Guimarães de Freitas Matos (UNIVAP - Universidade do Vale do Paraíba) ; Cláudia Barbosa Ladeira de Campos (UNIVAP - Universidade do Vale do Paraíba)

Abstract

Paracoccidioidemycosis is a prevalent systemic mycosis in Latin America. It is caused by the etiological agent Paracoccidioides brasiliensis, which forms a group called dimorphic fungi, together with five other phylogenetically related fungi. They are so called because they suffer a change in morphology inside host´s body. In the environment, they live as hyphal molds (mycelium) and convert to a pathogenic yeast form in the host´s lungs. The P. brasiliensis morphological transition (M-Y phase transition) can be induced in vitro by switching the incubation temperature from 25°C to 37°C. The morphological switch can be, therefore, considered as a kind of heat-shock response. In this way, we postulated that Hsp-90, a heat-shock protein, could be involved in P. brasilisensis M-Y phase transition. In order to test our hypothesis we treated P. brasiliensis with Geldanamycin (GdA), an Hsp-90 inhibitor, during M-Y phase transition as well as the yeast and mycelial phases. We noticed that treatment with GdA caused a dose-dependent inhibition of P. brasilisensis yeast proliferation, but this inhibition is not observed in the mycelial phase. We also observed that Hsp-90 inhibition by GdA blocks M-Y transition in a dose-dependent manner. It has been shown that calcineurin is a client protein of Hsp-90 in many different biological systems. In this way, we combined GdA and ciclosporin A (CsA), a calcineurin inhibitor, to treat P. brasiliensis during M-Y phase transition in order to test whether these proteins could be interacting in P. brasiliensis model system. We show that at low concentrations, these drugs separately have a small effect over M-Y phase transition, but presented a much greater effect when combined and completely block transition. So, in this work, we conclude that HSP-90 plays an important role in P. brasiliensis M-Y phase transition, helping in the fungus adaptation when submitted to a heat stress, probably not only in the culture but also inside host´s body. We also conclude that Hsp-90 activity is dependent on calcineurin activity, and we suggest that these proteins may be linked in a pathway that governs M-Y phase transition.਀匀甀瀀瀀漀爀琀攀搀戀礀䘀愀瀀攀猀瀀Ⰰ 䌀一倀焀愀渀搀䌀愀瀀攀猀⸀

Keyword: Dimorphism, Hsp-90, Calcineurin, mycelium, yeast

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