Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1993 Dec;37(12):2571–2577. doi: 10.1128/aac.37.12.2571

Effect of clindamycin on intracellular replication, protein synthesis, and infectivity of Toxoplasma gondii.

J Blais 1, C Tardif 1, S Chamberland 1
PMCID: PMC192741  PMID: 7509143

Abstract

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.

Full text

PDF
2571

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Araujo F. G., Huskinson J., Remington J. S. Remarkable in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrob Agents Chemother. 1991 Feb;35(2):293–299. doi: 10.1128/aac.35.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Araujo F. G., Remington J. S. Effect of clindamycin on acute and chronic toxoplasmosis in mice. Antimicrob Agents Chemother. 1974 Jun;5(6):647–651. doi: 10.1128/aac.5.6.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blais J., Garneau V., Chamberland S. Inhibition of Toxoplasma gondii protein synthesis by azithromycin. Antimicrob Agents Chemother. 1993 Aug;37(8):1701–1703. doi: 10.1128/aac.37.8.1701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chamberland S., Current W. L. Use of mouse macrophage cell lines for in vitro propagation of Toxoplasma gondii RH tachyzoites. Proc Soc Exp Biol Med. 1991 Jun;197(2):150–157. doi: 10.3181/00379727-197-43237. [DOI] [PubMed] [Google Scholar]
  5. Chamberland S., Kirst H. A., Current W. L. Comparative activity of macrolides against Toxoplasma gondii demonstrating utility of an in vitro microassay. Antimicrob Agents Chemother. 1991 May;35(5):903–909. doi: 10.1128/aac.35.5.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dannemann B. R., Israelski D. M., Remington J. S. Treatment of toxoplasmic encephalitis with intravenous clindamycin. Arch Intern Med. 1988 Nov;148(11):2477–2482. [PubMed] [Google Scholar]
  7. Dannemann B. R., McCutchan J. A., Israelski D. M., Antoniskis D., Leport C., Luft B. J., Chiu J., Vildé J. L., Nussbaum J. N., Orellana M. Treatment of acute toxoplasmosis with intravenous clindamycin. The California Collaborative Treatment Group. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):193–195. doi: 10.1007/BF01964461. [DOI] [PubMed] [Google Scholar]
  8. Decoster A., Darcy F., Capron A. Recognition of Toxoplasma gondii excreted and secreted antigens by human sera from acquired and congenital toxoplasmosis: identification of markers of acute and chronic infection. Clin Exp Immunol. 1988 Sep;73(3):376–382. [PMC free article] [PubMed] [Google Scholar]
  9. Derouin F., Nalpas J., Chastang C. Mesure in vitro de l'effet inhibiteur de macrolides, lincosamides et synergestines sur la croissance de Toxoplasma gondii. Pathol Biol (Paris) 1988 Dec;36(10):1204–1210. [PubMed] [Google Scholar]
  10. Filice G. A., Pomeroy C. Effect of clindamycin on pneumonia from reactivation of Toxoplasma gondii infection in mice. Antimicrob Agents Chemother. 1991 Apr;35(4):780–782. doi: 10.1128/aac.35.4.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Foppa C. U., Bini T., Gregis G., Lazzarin A., Esposito R., Moroni M. A retrospective study of primary and maintenance therapy of toxoplasmic encephalitis with oral clindamycin and pyrimethamine. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):187–189. doi: 10.1007/BF01964458. [DOI] [PubMed] [Google Scholar]
  12. Furtado G. C., Slowik M., Kleinman H. K., Joiner K. A. Laminin enhances binding of Toxoplasma gondii tachyzoites to J774 murine macrophage cells. Infect Immun. 1992 Jun;60(6):2337–2342. doi: 10.1128/iai.60.6.2337-2342.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Garin J. P., Paillard B. Toxoplasmose expérimentale de la souris. Activité comparée de: clindamycine, midécamycine, josamycine, spiramycine, pyriméthamine-sulfadoxine, et triméthoprime-sulfaméthoxazole. Ann Pediatr (Paris) 1984 Nov;31(10):841–845. [PubMed] [Google Scholar]
  14. Hand W. L., Boozer R. M., King-Thompson N. L. Antibiotic uptake by alveolar macrophages of smokers. Antimicrob Agents Chemother. 1985 Jan;27(1):42–45. doi: 10.1128/aac.27.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hand W. L., King-Thompson N. L., Steinberg T. H. Interactions of antibiotics and phagocytes. J Antimicrob Chemother. 1983 Oct;12 (Suppl 100):1–11. doi: 10.1093/jac/12.suppl_c.1. [DOI] [PubMed] [Google Scholar]
  16. Harris C., Salgo M. P., Tanowitz H. B., Wittner M. In vitro assessment of antimicrobial agents against Toxoplasma gondii. J Infect Dis. 1988 Jan;157(1):14–22. doi: 10.1093/infdis/157.1.14. [DOI] [PubMed] [Google Scholar]
  17. Hofflin J. M., Remington J. S. Clindamycin in a murine model of toxoplasmic encephalitis. Antimicrob Agents Chemother. 1987 Apr;31(4):492–496. doi: 10.1128/aac.31.4.492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jones T. C., Hirsch J. G. The interaction between Toxoplasma gondii and mammalian cells. II. The absence of lysosomal fusion with phagocytic vacuoles containing living parasites. J Exp Med. 1972 Nov 1;136(5):1173–1194. doi: 10.1084/jem.136.5.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jones T. C., Yeh S., Hirsch J. G. The interaction between Toxoplasma gondii and mammalian cells. I. Mechanism of entry and intracellular fate of the parasite. J Exp Med. 1972 Nov 1;136(5):1157–1172. doi: 10.1084/jem.136.5.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Katlama C. Evaluation of the efficacy and safety of clindamycin plus pyrimethamine for induction and maintenance therapy of toxoplasmic encephalitis in AIDS. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):189–191. doi: 10.1007/BF01964459. [DOI] [PubMed] [Google Scholar]
  21. Klempner M. S., Styrt B. Clindamycin uptake by human neutrophils. J Infect Dis. 1981 Nov;144(5):472–479. doi: 10.1093/infdis/144.5.472. [DOI] [PubMed] [Google Scholar]
  22. Leport C., Bastuji-Garin S., Perronne C., Salmon D., Marche C., Briçaire F., Vilde J. L. An open study of the pyrimethamine-clindamycin combination in AIDS patients with brain toxoplasmosis. J Infect Dis. 1989 Sep;160(3):557–558. doi: 10.1093/infdis/160.3.557. [DOI] [PubMed] [Google Scholar]
  23. Mack D. G., McLeod R. New micromethod to study the effect of antimicrobial agents on Toxoplasma gondii: comparison of sulfadoxine and sulfadiazine individually and in combination with pyrimethamine and study of clindamycin, metronidazole, and cyclosporin A. Antimicrob Agents Chemother. 1984 Jul;26(1):26–30. doi: 10.1128/aac.26.1.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McCabe R. E., Oster S. Current recommendations and future prospects in the treatment of toxoplasmosis. Drugs. 1989 Dec;38(6):973–987. doi: 10.2165/00003495-198938060-00008. [DOI] [PubMed] [Google Scholar]
  25. Pfefferkorn E. R., Nothnagel R. F., Borotz S. E. Parasiticidal effect of clindamycin on Toxoplasma gondii grown in cultured cells and selection of a drug-resistant mutant. Antimicrob Agents Chemother. 1992 May;36(5):1091–1096. doi: 10.1128/aac.36.5.1091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Piens M. A., Garin J. P. New perspectives in the chemoprophylaxis of toxoplasmosis. J Chemother. 1989 Feb;1(1):46–51. doi: 10.1080/1120009x.1989.11738863. [DOI] [PubMed] [Google Scholar]
  27. Proctor R. A., Olbrantz P. J., Mosher D. F. Subinhibitory concentrations of antibiotics alter fibronectin binding to Staphylococcus aureus. Antimicrob Agents Chemother. 1983 Nov;24(5):823–826. doi: 10.1128/aac.24.5.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rolston K. V. Treatment of acute toxoplasmosis with oral clindamycin. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):181–183. doi: 10.1007/BF01964456. [DOI] [PubMed] [Google Scholar]
  29. Ruf B., Pohle H. D. Role of clindamycin in the treatment of acute toxoplasmosis of the central nervous system. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):183–186. doi: 10.1007/BF01964457. [DOI] [PubMed] [Google Scholar]
  30. Seaberg L. S., Parquette A. R., Gluzman I. Y., Phillips G. W., Jr, Brodasky T. F., Krogstad D. J. Clindamycin activity against chloroquine-resistant Plasmodium falciparum. J Infect Dis. 1984 Dec;150(6):904–911. doi: 10.1093/infdis/150.6.904. [DOI] [PubMed] [Google Scholar]
  31. Sibley L. D., Krahenbuhl J. L., Adams G. M., Weidner E. Toxoplasma modifies macrophage phagosomes by secretion of a vesicular network rich in surface proteins. J Cell Biol. 1986 Sep;103(3):867–874. doi: 10.1083/jcb.103.3.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sibley L. D., Krahenbuhl J. L. Modification of host cell phagosomes by Toxoplasma gondii involves redistribution of surface proteins and secretion of a 32 kDa protein. Eur J Cell Biol. 1988 Oct;47(1):81–87. [PubMed] [Google Scholar]
  33. Tabbara K. F., Nozik R. A., O'Connor G. R. Clindamycin effects on experimental ocular toxoplasmosis in the rabbit. Arch Ophthalmol. 1974 Sep;92(3):244–247. doi: 10.1001/archopht.1974.01010010252017. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES