Hsp90 regulates Paracoccidioides brasiliensis proliferation and ROS levels under thermal stress and cooperates with calcineurin to control yeast to mycelium dimorphism

Hsp90 regulates Paracoccidioides brasiliensis proliferation and ROS levels under thermal stress and cooperates with calcineurin to control yeast to mycelium dimorphism

Author Matos, Tatiana G. F. Google Scholar
Morais, Flavia V. Google Scholar
Campos, Claudia Barbosa Ladeira de Autor UNIFESP Google Scholar
Institution Univ Vale Parailba UNIVAP
Universidade Federal de São Paulo (UNIFESP)
Abstract Paracoccidioidomycosis is a systemic human mycosis in Latin America caused by Paracoccidioides brasiliensis, a dimorphic pathogenic fungus that lives as a mold in the environment and as yeast during infections of human lungs. in this work, we provide evidence that the inhibition of Hsp90 by geldanamycin (GDA) impairs the proliferation of the yeast, but has no effect on mycelial development. Treatment with cyclosporin A (CsA), an inhibitor of the Hsp90 client protein calcineurin, did not increase the effect of GDA. in contrast, GDA prevented mycelial to yeast differentiation through a mechanism partially dependent on calcineurin, whereas differentiation from yeast to mycelia occurred independent of GDA or CsA. A significant increase in reactive oxygen species (ROS) levels was detected in GDA-treated yeast at 42 degrees C. However, the levels of ROS remained unchanged in GDA-treated yeast or mycelia incubated at 37 degrees C, suggesting that Hsp90 plays different roles under normal and thermal stress conditions. We propose that Hsp90 strengthens the stress response of P. brasiliensis at 37 degrees C through a mechanism that does not involve ROS. Moreover, we suggest that Hsp90 has calcineurin-dependent functions in this organism
Keywords Paracoccidioides brasiliensis
Hsp90
calcineurin
thermal stress
dimorphism
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 10/50078-8
Date 2013-05-01
Published in Medical Mycology. London: Informa Healthcare, v. 51, n. 4, p. 413-421, 2013.
ISSN 1369-3786 (Sherpa/Romeo, impact factor)
Publisher Informa Healthcare
Extent 413-421
Origin http://dx.doi.org/10.3109/13693786.2012.725481
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000317592600010
URI http://repositorio.unifesp.br/handle/11600/36264

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