Recombinant bactericidal/permeability-increasing protein (rBPI(21)) in combination with sulfadiazine is active against Toxoplasma gondii

The activity of recombinant bactericidal/permeability-increasing protein (r BPI(21)), alone or in combination with sulfadiazine, on the intracellular r eplication of Toxoplasma gondii was assessed in vitro and in mice with acut e toxoplasmosis. rBPI(21) markedly inhibited the intracellular growth of T. gondii in human foreskin fibroblasts (HFFs), Following 72 h of exposure, t he 50% inhibitory concentration of rBPI(21) for T. gondii was 2.6 mu g/ml, whereas only slight cytotoxicity for HFF cells was observed at the concentr ations tested. Subsequent mathematical analyses revealed that the combinati on of rBPI(21) with sulfadiazine yielded slight to moderate synergistic eff ects against T. gondii in vitro. Infection of mice orally with C56 cysts or intraperitoneally (i.p.) with RM tachyzoites resulted in 100% mortality, w hereas prolongation of the time to death or significant survival (P = 0.002 ) was noted for those animals treated with 5 to 20 mg of rBPI(21) per kg of body weight per day, Treatment with rBPI(21) in combination with sulfadiaz ine resulted in significant (P = 0.0001) survival of mice infected i.p. wit h tachyzoites but not of mice infected orally with T. gondii cysts. These r esults indicate that rBPI(21) is active in vitro and in vivo against T. gon dii and that its activity is significantly enhanced when it is used in comb ination with sulfadiazine, To our knowledge, this is the first report of th e activity of rBPI(21) against a protozoan parasite.