Characterization of Major Surface Protease Homologues ofTrypanosoma congolense

Abstract

Trypanosomes encode a family of proteins known as Major Surface Metalloproteases (MSPs). We have identified six putative MSPs encoded within the partially sequencedT. congolensegenome. Phylogenic analysis indicates thatT. congolenseMSPs belong to five subfamilies that are conserved among African trypanosome species. Molecular modeling, based on the known structure ofLeishmania MajorGP63, reveals subfamily-specific structural variations around the putative active site despite conservation of overall structure, suggesting that each MSP subfamily has evolved to recognize distinct substrates. We have cloned and purified a protein encoding the amino-terminal domain of theT. congolensehomologue TcoMSP-D (most closely related toLeishmaniaGP63). We detect TcoMSP-D in the serum ofT. congolense-infected mice. Mice immunized with the amino-terminal domain of TcoMSP-D generate a persisting IgG1 antibody response. Surprisingly, a low-dose challenge of immunized mice withT. congolensesignificantly increases susceptibility to infection, indicating that immunity to TcoMSP-D is a factor affecting virulence.