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Hsp90 regulates Paracoccidioides brasiliensis proliferation and ROS levels under thermal stress and cooperates with calcineurin to control yeast to mycelium dimorphism.
Med Mycol. 2013 May; 51(4):413-21.MM

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°C. However, the levels of ROS remained unchanged in GDA-treated yeast or mycelia incubated at 37°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°C through a mechanism that does not involve ROS. Moreover, we suggest that Hsp90 has calcineurin-dependent functions in this organism.

Authors+Show Affiliations

Instituto de Pesquisa e Desenvolvimento , Universidade do Vale do ParaiIba UNIVAP, São Jose dos Campos, São Paulo, Brazil.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23013413

Citation

Matos, Tatiana G F., et al. "Hsp90 Regulates Paracoccidioides Brasiliensis Proliferation and ROS Levels Under Thermal Stress and Cooperates With Calcineurin to Control Yeast to Mycelium Dimorphism." Medical Mycology, vol. 51, no. 4, 2013, pp. 413-21.
Matos TG, Morais FV, Campos CB. Hsp90 regulates Paracoccidioides brasiliensis proliferation and ROS levels under thermal stress and cooperates with calcineurin to control yeast to mycelium dimorphism. Med Mycol. 2013;51(4):413-21.
Matos, T. G., Morais, F. V., & Campos, C. B. (2013). Hsp90 regulates Paracoccidioides brasiliensis proliferation and ROS levels under thermal stress and cooperates with calcineurin to control yeast to mycelium dimorphism. Medical Mycology, 51(4), 413-21. https://doi.org/10.3109/13693786.2012.725481
Matos TG, Morais FV, Campos CB. Hsp90 Regulates Paracoccidioides Brasiliensis Proliferation and ROS Levels Under Thermal Stress and Cooperates With Calcineurin to Control Yeast to Mycelium Dimorphism. Med Mycol. 2013;51(4):413-21. PubMed PMID: 23013413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hsp90 regulates Paracoccidioides brasiliensis proliferation and ROS levels under thermal stress and cooperates with calcineurin to control yeast to mycelium dimorphism. AU - Matos,Tatiana G F, AU - Morais,Flavia V, AU - Campos,Claudia B L, Y1 - 2012/09/27/ PY - 2012/9/28/entrez PY - 2012/9/28/pubmed PY - 2015/1/15/medline SP - 413 EP - 21 JF - Medical mycology JO - Med Mycol VL - 51 IS - 4 N2 - 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°C. However, the levels of ROS remained unchanged in GDA-treated yeast or mycelia incubated at 37°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°C through a mechanism that does not involve ROS. Moreover, we suggest that Hsp90 has calcineurin-dependent functions in this organism. SN - 1460-2709 UR - https://www.unboundmedicine.com/medline/citation/23013413/Hsp90_regulates_Paracoccidioides_brasiliensis_proliferation_and_ROS_levels_under_thermal_stress_and_cooperates_with_calcineurin_to_control_yeast_to_mycelium_dimorphism_ L2 - https://academic.oup.com/mmy/article-lookup/doi/10.3109/13693786.2012.725481 DB - PRIME DP - Unbound Medicine ER -