Schistosoma mansoni: developmental arrest of miracidia treated with histone deacetylase inhibitors.
In the present study, we examined the effect of the histone deacetylase (HDAC) inhibitors trichostatin A (TSA), valproic acid (VA) and sodium-butyrate on the metamorphosis of larvae of the human blood-fluke Schistosoma mansoni from the free-swimming miracidia into the intramolluskal sporocyst. We show that HDAC inhibitors block transformation in concentration dependant manner. TSA reversibly blocks this developmental process: only 13+/-11% of TSA treated miracidia transform into sporocysts in-vitro, compared to 92+/-3% in the mock-treated control. Other enzyme inhibitors such as cycloheximide or hydroxyurea had no effect on metamorphosis. For treatment of up to 4 h, the effect of TSA was completely reversible. Our data indicates that HDAC activity is necessary for the transformation of S. mansoni miracidia during infection of the snail host.
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Parasitologie Fonctionnelle et Evolutive, UMR 5244 CNRS/Université de Perpignan/EPHE, 52, Avenue Paul Alduy, 66860 Perpignan, France.
Cosseau
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Grunau
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D000818:Animals; D001700:Biomphalaria / Q000469:parasitology; D002087:Butyrates / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D008647:Mesocricetus; D008675:Metamorphosis, Biological / Q000187:drug effects*; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000254:growth & development; D014635:Valproic Acid / Q000494:pharmacology
D002087:Butyrates; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; D014635:Valproic Acid