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Eukaryotic Cell, December 2002, p. 936-943, Vol. 1, No. 6
1535-9778/02/$04.00+0     DOI: 10.1128/EC.1.6.936-943.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Inhibition of HSP90 in Trypanosoma cruzi Induces a Stress Response but No Stage Differentiation

Sebastian E. B. Graefe,1 Martina Wiesgigl,2 Iris Gaworski,1 Andrea Macdonald,2 and Joachim Clos2*

Department of Medical Microbiology and Immunology,1 Parasitology Section, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany2

Received 28 May 2002/ Accepted 5 August 2002

The 90-kDa heat shock proteins (HSP90) are important in the regulation of numerous intracellular processes in eukaryotic cells. In particular, HSP90 has been shown to be involved in the control of the cellular differentiation of the protozoan parasite Leishmania donovani. We investigated the role of HSP90 in the related parasite Trypanosoma cruzi by inhibiting its function using geldanamycin (GA). GA induced a dose-dependent increase in heat shock protein levels and a dose-dependent arrest of proliferation. Epimastigotes were arrested in G1 phase of the cell cycle, but no stage differentiation occurred. Blood form trypomastigotes showed conversion towards spheromastigote-like forms when they were cultivated with GA, but differentiation into epimastigotes was permanently blocked. We conclude that, similar to leishmanial HSP90, functional HSP90 is essential for cell division in T. cruzi and serves as a feedback inhibitor in the cellular stress response. In contrast to L. donovani cells, however, T. cruzi cells treated with GA do not begin to differentiate into relevant life cycle stages.

* Corresponding author. Mailing address: Bernard Nocht Institute for Tropical Medecine, 20359 Hamburg, Germany. Phone: 49 40 42818 481. Fax: 49 40 42818 512. E-mail: clos{at}bni-hamburg.de.

Eukaryotic Cell, December 2002, p. 936-943, Vol. 1, No. 6
1535-9778/02/$04.00+0     DOI: 10.1128/EC.1.6.936-943.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.





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Appl. Environ. Microbiol. Infect. Immun. J. Bacteriol.
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Copyright © 2002 by the American Society for Microbiology.