Recombinant bactericidal/permeability-increasing protein (rBPI21) in combination with sulfadiazine is active against Toxoplasma gondii.
The activity of recombinant bactericidal/permeability-increasing protein (rBPI21), alone or in combination with sulfadiazine, on the intracellular replication of Toxoplasma gondii was assessed in vitro and in mice with acute toxoplasmosis. rBPI21 markedly inhibited the intracellular growth of T. gondii in human foreskin fibroblasts (HFFs). Following 72 h of exposure, the 50% inhibitory concentration of rBPI21 for T. gondii was 2.6 micrograms/ml, whereas only slight cytotoxicity for HFF cells was observed at the concentrations tested. Subsequent mathematical analyses revealed that the combination of rBPI21 with sulfadiazine yielded slight to moderate synergistic effects against T. gondii in vitro. Infection of mice orally with C56 cysts or intraperitoneally (i.p.) with RH tachyzoites resulted in 100% mortality, whereas prolongation of the time to death or significant survival (P = 0.002) was noted for those animals treated with 5 to 20 mg of rBPI21 per kg of body weight per day. Treatment with rBPI21 in combination with sulfadiazine resulted in significant (P = 0.0001) survival of mice infected i.p. with tachyzoites but not of mice infected orally with T. gondii cysts. These results indicate that rBPI21 is active in vitro and in vivo against T. gondii and that its activity is significantly enhanced when it is used in combination with sulfadiazine. To our knowledge, this is the first report of the activity of rBPI21 against a protozoan parasite.
Khan
A A
AA
Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, California 94301, USA.
Lambert
L H
LH
Remington
J S
JS
Araujo
F G
FG
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001798:Blood Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013411:Sulfadiazine / Q000494:pharmacology* / Q000627:therapeutic use; D014122:Toxoplasma / Q000187:drug effects*; D014124:Toxoplasmosis, Animal / Q000188:drug therapy
D023181:Antimicrobial Cationic Peptides; D000981:Antiprotozoal Agents; D001798:Blood Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C021623:bactericidal permeability increasing protein; D013411:Sulfadiazine