Effect of clindamycin on intracellular replication, protein synthesis, and infectivity of Toxoplasma gondii.
We studied the effects of clindamycin and a combination of clindamycin and pyrimethamine on the proliferation of Toxoplasma gondii in cultured mammalian cells and the effect of clindamycin on the parasite's RNA and protein syntheses. Infected macrophages were treated for 48 h with clindamycin or a combination of clindamycin and pyrimethamine, and the 50% inhibitory concentrations for parasite growth were 32.50 +/- 1.30 and 10.78 +/- 0.56 micrograms/ml, respectively. A modified susceptibility assay was also used to measure the effect of low concentrations of clindamycin on T. gondii. Macrophages and bovine turbinate cells were infected with low numbers of tachyzoites and were exposed to low concentrations of clindamycin for 5 days. In these systems, a concentration of 10 ng of clindamycin per ml inhibited 50% of the growth of the parasite in macrophages, while it completely prohibited the growth of the parasite in epithelial cells. When free tachyzoites were preexposed to clindamycin for 4 h, the reduction of parasite infectivity was proportional to the amount of drug; 100 ng of clindamycin per ml reduced the infectivity of T. gondii to 46.5% +/- 8.5% of that of the untreated control. A concentration of 40 micrograms of clindamycin per ml reduced protein synthesis by 56.2% +/- 6.0% but had no effect on RNA synthesis after a 4-h exposure of free tachyzoites of T. gondii to the drug. Our results show that long-term exposure to low concentrations of clindamycin reduces the level of replication of T. gondii, that clindamycin affects the protein synthesis of free parasites, and that clindamycin impairs the ability of tachyzoites to infect host cells.
Blais
J
J
Laboratoire et Service d'Infectiologie, Centre de Recherche du Centre Hospitalier de l'Université Laval, Québec, Canada.
Tardif
C
C
Chamberland
S
S
D000818:Animals; D002981:Clindamycin / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D007424:Intracellular Fluid / Q000469:parasitology; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008826:Microbial Sensitivity Tests; D015800:Protozoan Proteins / Q000096:biosynthesis*; D011739:Pyrimethamine / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D013997:Time Factors; D014122:Toxoplasma / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014124:Toxoplasmosis, Animal / Q000188:drug therapy
D015800:Protozoan Proteins; D002981:Clindamycin; D012313:RNA; D011739:Pyrimethamine