Phenotypic characterization of Leishmania mexicana pentamidine-resistant promastigotes. Modulation of the resistance during in-vitro developmental life cycle.
Two clones of Leishmania mexicana resistant to 5 microM (LmR5CL2) and 20 microM (LmR20CL1) pentamidine, derived from a parental wild-type clone (LmWTCL3) were selected in vitro using a continuous drug pressure protocol. Both resistant clones expressed a cross-resistance to diminazene aceturate. No differences in their in-vitro infectivity for mouse peritoneal macrophages between wild-type and pentamidine-resistant promastigotes were observed. During these experiments, promastigotes of LmR20CL1 derived from intramacrophagic amastigote forms reverted to the pentamidine-sensitive phenotype, unlike the lower resistant ones. In the same way, when a complete developmental sequence of L. mexicana was achieved in axenic cultures, LmR20CL1 promastigotes derived from axenically growing amastigotes expressed an IC50 value close to the wild-type one, whereas resulting LmR5CL2 promastigotes remained pentamidine resistant. This modulation of the chemoresistance during the developmental life cycle could be significant in the transmission of drug-resistant strains by Phlebotominae as well as in basic research to follow drug resistance during the in-vitro and in-vivo life cycle of Leishmania.
Sereno
D
D
Laboratoire de biologie parasitaire, Orstom, Montpellier, France.
Michon
P
P
Brajon
N
N
Lemesre
J L
JL
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002999:Clone Cells / Q000187:drug effects; D004351:Drug Resistance; D066298:In Vitro Techniques; D007894:Leishmania mexicana / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D008018:Life Cycle Stages; D051379:Mice; D010419:Pentamidine / Q000494:pharmacology*; D010641:Phenotype
D000981:Antiprotozoal Agents; D010419:Pentamidine