Recombinant Bactericidal/Permeability-Increasing Protein (rBPI 21 ) in Combination with Sulfadiazine Is Active against Toxoplasma gondii

Abstract

ABSTRACT The activity of recombinant bactericidal/permeability-increasing protein (rBPI 21 ), alone or in combination with sulfadiazine, on the intracellular replication of Toxoplasma gondii was assessed in vitro and in mice with acute toxoplasmosis. rBPI 21 markedly inhibited the intracellular growth of T. gondii in human foreskin fibroblasts (HFFs). Following 72 h of exposure, the 50% inhibitory concentration of rBPI 21 for T. gondii was 2.6 μg/ml, whereas only slight cytotoxicity for HFF cells was observed at the concentrations tested. Subsequent mathematical analyses revealed that the combination of rBPI 21 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 rBPI 21 per kg of body weight per day. Treatment with rBPI 21 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 rBPI 21 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 rBPI 21 against a protozoan parasite.