Biochemistry of Pentostam resistant Leishmania.
Promastigotes of Leishmania mexicana amazonensis WR 669 clone 4 were made resistant to antimony in the form of Pentostam (sodium stibogluconate) by exposure to media containing increasing concentrations of Sb. The dose of Sb expected to kill 50% of promastigotes and amastigotes of the parent sensitive clone (WR 669) and the resistant clone (WR 669R) was determined by exposure of suspensions in physiologic salt solution for 3 hr. The approximate Ed50s in microgram Sb/ml were: 10,000 for WR 669R promastigotes; 7,000 for WR 669R amastigotes; 200 for WR 669 promastigotes; and 150 for WR 669 amastigotes. Thus, Sb resistance and Sb sensitivity expressed by promastigote clones are also expressed by their respective amastigotes. Studies with 125Sb-Pentostam showed that WR 669R amastigote resistance was not due to altered Sb uptake over 1 hr. When amastigotes pretreated with Pentostam were incubated with 14C labeled metabolic precursors, susceptibility to Sb was correlated with inhibition of glycolytic enzymes and of fatty acid beta-oxidation.
Berman
J D
JD
Walter Reed Army Institute of Research, Division of Experimental Therapeutics, Washington, DC.
Edwards
N
N
King
M
M
Grogl
M
M
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance; D005942:Gluconates / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects* / Q000378:metabolism
D005942:Gluconates; D000967:Antimony Sodium Gluconate