Praziquantel binds Schistosoma mansoni adult worm actin

Abstract

Praziquantel (PZQ) is widely used for the treatment of schistosomiasis. It induces worm muscle contractions and tegumental disruption, followed by exposure of parasite surface membrane antigens to the host immunological defence mechanisms. It may be assumed that PZQ, like cholesterol, is too hydrophobic to traverse the schistosome outer lipid bilayers by passive diffusion and probably requires binding to a surface membrane protein carrier for distribution throughout the worm. However, the PZQ binding site on the schistosome surface and the precise mechanism of action are not yet known. The Claisen condensation reaction was used to bind PZQ on cellulose acetate membranes. Triton-insoluble surface membrane antigens of Schistosoma mansoni adult worms were allowed to bind to the PZQ column. The identity of the bound molecules was examined by amino acid microsequencing and immunogenicity in outbred and inbred mice. The PZQ column was found to bind molecules of 45 kDa selectively from the Triton-insoluble surface membrane antigens of S. mansoni adult worms. Amino acid microsequencing revealed that the 45 kDa species consist predominantly of schistosome actin. This finding was supported by the poor immunogenicity of the 45 kDa molecules in outbred and inbred mice. PZQ was also shown to bind bovine actin but not bovine serum albumin. However, pre-incubation with bovine actin did not impair the effect of PZQ on adult worms in vitro. The study represents an attempt to understand how PZQ distributes across schistosome outer lipid bilayers.