XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:110-2

Poster (Painel)

110-2

Inhibition of Calcineurin by Cyclosporin A and of HSP90 with Geldanamycin Change the Overall Lipids Constituents in Yeasts of Paracoccidioides brasiliensis

Authors:

Tatiana Guimarães de Freitas Matos (UNIVAP - Universidade do Vale do Paraíba) ; Adriana Carvalho de Souza (UNIVAP - Universidade do Vale do Paraíba) ; Leandro José Raniero (UNIVAP - Universidade do Vale do Paraíba) ; Rosana Maria Alberici (UNICAMP - Universidade Estadual de Campinas) ; Marcos Nogueira Eberlin (UNICAMP - Universidade Estadual de Campinas) ; Luciane Carla Alberici (USP - Universidade de São Paulo) ; Cláudia Barbosa Ladeira de Campos (UNIVAP - Universidade do Vale do Paraíba)

Abstract

Paracoccidioides brasiliensis is a dimorphic fungus that causes paracoccidioidomycosis, the most prevalent human deep mycosis in Latin America. We have previously shown that either calcineurin inhibition by cyclosporin A (CSA) or HSP90 inhibition by geldanamycin (GdA) in P. brasiliensis cultured in YPD medium prevented yeast cells proliferation and induced intracellular accumulation of lipid vesicles. Here we show that accumulation of vesicles were dependent on the culture media, since culturing yeasts of P. brasiliensis with F12 defined media did not change the amount or size of the intracellular lipid vesicles in yeast cells treated or not with different concentration of CsA or GdA. However, the overall lipid constituents of the cells and of the isolated vesicles completely changed after treatment with either drug. FT-IR analysis found consistent differences of lipid content between lipid vesicles form control yeasts and yeasts treated with CSA or GdA. Analysis of lipids of isolated vesicles by easy ambient sonic-spray ionization mass spectrometry (EASI-MS) showed that CSA and GdA differentially change the relative composition of triglycerides, phospholipids and diacylglycerol ions in yeasts. In order to investigate whether the content of theses vesicles could be secreted to induce any phenotypic response in the population of yeast of P. brasiliensis, we cultured yeast cells with vesicles isolated from yeasts treated under different condition and showed that vesicles from CsA-treated yeast cells inhibited growth of the culture, but the vesicles from GdA-treated yeast cells did not. Vesicles purified from yeast cells under different conditions produced no effect on Candida albicans. We suggest a role for calcineurin and HSP90 in regulation of lipid metabolism in Paracoccidioides brasiliensis in yeast forms. However, considering that calcineurin has been described as being a client protein of HSP90 in vertebrates and fungi and that these enzymes can share some of their roles in these organism, our results suggest that they might have both convergent and divergent roles in lipid metabolism in Paracoccidioides brasiliensis. The function of these lipid vesicles in different fields of fungal biology remains to be determined. ਀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: Calcineurin, Hsp-90, Lipids, Vesicles

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