Antimony resistance and trypanothione in experimentally selected and clinical strains of Leishmania panamensis.
The participation of trypanothione in clinical and experimental antimony (Sb) resistance in Leishmania panamensis was examined by using specific inhibitors. Buthionine sulfoximine (BSO) significantly reversed the resistance to trivalent Sb (Sb(III)) of promastigotes of experimentally derived Sb-resistant lines, supporting the participation of a trypanothione-mediated mechanism of resistance. In contrast, promastigotes of strains isolated at the time of clinical treatment failure and resistant to pentavalent Sb (Sb(V)) as intracellular amastigotes were not cross resistant to Sb(III), and BSO had little or no effect on susceptibility. Difluoromethylornithine did not alter the Sb(III) susceptibilities of experimentally selected lines or clinical strains. The mechanisms of acquired resistance emerging in clinical settings may differ from those selected by in vitro exposure to Sb.
Goyeneche-Patino
Diego A
DA
Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Avenida 1 Norte # 3-03, Cali, Colombia.
Valderrama
Liliana
L
Walker
John
J
Saravia
Nancy G
NG
D000818:Animals; D000965:Antimony / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004351:Drug Resistance; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007891:Leishmania / Q000145:classification / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D007896:Leishmaniasis / Q000188:drug therapy / Q000469:parasitology*; D021261:Parasitic Sensitivity Tests; D013095:Spermidine / Q000031:analogs & derivatives* / Q000378:metabolism
D000981:Antiprotozoal Agents; D019328:Buthionine Sulfoximine; C044809:trypanothione; D000965:Antimony; D005978:Glutathione; D013095:Spermidine