Journal Article

Transcriptional profile of <i>ras1</i> and <i>ras2</i> and the potential role of farnesylation in the dimorphism of the human pathogen <i>Paracoccidioides brasiliensis</i>

Larissa Fernandes, Hugo C. Paes, Aldo H. Tavares, Simoneide S. Silva, Alessandra Dantas, Célia M.A. Soares, Fernando A.G. Torres and Maria Sueli S. Felipe

in FEMS Yeast Research

Volume 8, issue 2, pages 300-310
Published in print March 2008 |
Published online October 2007 | e-ISSN: 1567-1364 | DOI: http://dx.doi.org/10.1111/j.1567-1364.2007.00317.x

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Abstract

Paracoccidioides brasiliensis is a thermo-dimorphic fungus that causes a human systemic mycosis with high incidence in Latin America. Owing to their participation in the control of pathogen morphogenesis, differentiation and virulence, it was decided to characterize ras genes in P. brasiliensis. ras1 and ras2 were identified to be coding for two different proteins with high identity. The ras transcriptional pattern was investigated by reverse transcription PCR (RT-PCR) during mycelium-to-yeast (M→Y) transition, heat shock at 42 °C and after internalization of yeast cells by murine macrophages. Both genes were downregulated inside macrophages and ras1, at 42 °C. In contrast, ras genes did not show any transcriptional variation during the M→Y transition. The fact that Ras proteins are attached to the membrane via farnesylation prompted the use of a farnesyltransferase inhibitor to investigate the importance of this process for vegetative growth and dimorphic transition. Farnesylation blockage interfered with the vegetative growth of yeast cells and stimulated germinative tube production even at 37 °C. During Y→M transition, the inhibitor increased filamentation in a dose-dependent manner, indicating that impaired farnesylation favours the mycelium form of P. brasiliensis. The results suggest that ras genes might have a role in dimorphism, heat shock response and in host–pathogen interaction.

Keywords: Ras; farnesylation; dimorphism; heat shock response; host–pathogen interaction; Paracoccidioides brasiliensis

Journal Article.  6714 words.  Illustrated.

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