Serine protease inhibitors block invasion of host cells by Toxoplasma gondii.
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 microM, 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.
Conseil
V
V
Unité 42 INSERM. IBL, Institut Pasteur de Lille, 59019 Lille Cedex, France.
Soête
M
M
Dubremetz
J F
JF
D000818:Animals; D002522:Chlorocebus aethiops; D003374:Coumarins / Q000494:pharmacology*; D049934:Isocoumarins; D012697:Serine Endopeptidases / Q000502:physiology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects* / Q000254:growth & development; D014709:Vero Cells
D003374:Coumarins; D049934:Isocoumarins; D015842:Serine Proteinase Inhibitors; D013450:Sulfones; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; C046235:3,4-dichloroisocoumarin; D012697:Serine Endopeptidases