Parasiticidal effect of clindamycin on Toxoplasma gondii grown in cultured cells and selection of a drug-resistant mutant.
Clindamycin, which has been reported to have no significant in vitro activity against Toxoplasma gondii, actually markedly inhibits the growth of this parasite in infected human fibroblasts. When measured 3 days after treatment, the concentration required to reduce parasite growth by 50% is about 1 ng/ml. Some observers failed to note this inhibition because of its markedly delayed onset. At 6 ng/ml, clindamycin is parasiticidal, and the rate and extent of parasite killing increase with higher drug concentrations. With the aid of chemical mutagenesis, we isolated a parasite mutant that is approximately 100-fold more resistant to clindamycin than is the wild type. Lincomycin inhibits T. gondii at a higher 50% inhibitory concentration, about 100 ng/ml. The clindamycin-resistant mutant is partially cross-resistant to lincomycin.
Pfefferkorn
E R
ER
Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755-3842.
Nothnagel
R F
RF
Borotz
S E
SE
D000818:Animals; D002478:Cells, Cultured; D002981:Clindamycin / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D008034:Lincomycin / Q000494:pharmacology; D009154:Mutation; D014122:Toxoplasma / Q000187:drug effects* / Q000235:genetics; D014316:Tritium
D014316:Tritium; D002981:Clindamycin; D008034:Lincomycin