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Antimicrobial Agents and Chemotherapy, June 1999, p. 1358-1361, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Serine Protease Inhibitors Block Invasion of Host Cells by Toxoplasma gondii

V. Conseil, M. Soête, and J. F. Dubremetz*

Unité 42 INSERM. IBL, Institut Pasteur de Lille, 59019 Lille Cedex, France

Received 16 November 1998/Returned for modification 1 February 1999/Accepted 19 March 1999

We investigated the effect of protease inhibitors on the asexual development of the protozoan parasite Toxoplasma gondii. Among the inhibitors tested only two irreversible serine protease inhibitors, 3,4-dichloroisocoumarin and 4-(2-aminoethyl)-benzenesulfonyl fluoride, clearly prevented invasion of the host cells by specifically affecting parasite targets in a dose-dependent manner, with 50% inhibitory concentrations between 1 and 5 and 50 and 100 µM, respectively. Neither compound significantly affected parasite morphology, basic metabolism, or gliding motility within the range of the experimental conditions in which inhibition of invasion was demonstrated. No partial invasion was observed, meaning that inhibition occurred at an early stage of the interaction. These results suggest that at least one serine protease of the parasite is involved in the invasive process of T. gondii.


* Corresponding author. Mailing address: Unité 42 INSERM. IBL, Institut Pasteur de Lille, 1 rue Calmette 59019 Lille Cedex, France. Phone: (33) 320 871 173. Fax: (33) 320 871 158. E-mail: jean-francois.dubremetz{at}pasteur-lille.fr.


Antimicrobial Agents and Chemotherapy, June 1999, p. 1358-1361, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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