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

Autor(es)

Matos, Tatiana G. F. ^[1] ; Morais, Flavia V. ^[1] ; Campos, Claudia B. L. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Vale Parailba UNIVAP, Inst Pesquisa & Desenvolvimento, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo UNIFESP, Inst Ciencia & Tecnol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Medical Mycology; v. 51, n. 4, p. 413-421, MAY 2013.
• Citações Web of Science: 10

Resumo

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 (AU)

• Processo FAPESP: 10/50078-8 - Calcineurina e cAMP/PKA na fisiologia e no estresse do fungo Paracoccidioides brasiliensis
• Beneficiário: Claudia Barbosa Ladeira de Campos
• Modalidade de apoio: Auxílio à Pesquisa - Regular