Selective killing of Leishmania amastigotes expressing a thymidine kinase suicide gene.
The thymidine kinase gene of Herpes simplex type-1 virus was transfected into several Leishmania species to create drug-sensitive mutants. Expression of the thymidine kinase gene is not by itself harmful to Leishmania cells but it is capable of phosphorylating ganciclovir, a nucleoside analog, into a highly toxic product. In addition to the generation of Leishmania promastigotes highly sensitive to ganciclovir, the thymidine kinase gene was expressed similarly by amastigotes engulfed either by murine or by human macrophages. Leishmania major amastigotes expressing thymidine kinase were eliminated by 85% when treated with ganciclovir. Selective killing of parasites expressing suicide genes at their infective stage could suggest novel strategies for controlling parasitic infections.
Muyombwe
A
A
Centre de Recherche en Infectiologie, CHUL, Faculté de Médecine, Université Laval, Québec, Canada.
Olivier
M
M
Ouellette
M
M
Papadopoulou
B
B
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015774:Ganciclovir / Q000378:metabolism / Q000494:pharmacology*; D005814:Genes, Viral; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection
D013937:Thymidine Kinase; D015774:Ganciclovir