Characterization of Major Surface Protease Homologues of Trypanosoma congolense

• Published in: BioMed research international 2010-01, Vol.2010 (2010), p.1-14
• Main Authors: Marcoux, Veronica, Wei, Guojian, Tabel, Henry, Bull, Harold J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analysis of Variance; Animals; Antibodies; Antibodies, Protozoan - metabolism; Antigens, Protozoan - genetics; Antigens, Protozoan - immunology; Antigens, Protozoan - metabolism; Bacteriology; Biotechnology; Colleges & universities; Disease Models, Animal; E coli; Female; Genomes; Immunoglobulin G - metabolism; Leishmania major; Livestock; Metalloproteases - genetics; Metalloproteases - immunology; Metalloproteases - metabolism; Metalloproteases - physiology; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Sequence Data; Molecular structure; Phylogeny; Proteins; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Protozoan Proteins - metabolism; Protozoan Proteins - physiology; Rabbits; Scholarships & fellowships; Sequence Alignment; Trypanosoma; Trypanosoma congolense; Trypanosoma congolense - enzymology; Trypanosome; Trypanosomiasis, African; Virulence
• ISSN: 1110-7243; 2314-6133; 1110-7251; 2314-6141
• DOI: 10.1155/2010/418157

Trypanosomes encode a family of proteins known as Major Surface Metalloproteases (MSPs). We have identified six putative MSPs encoded within the partially sequenced T. congolense genome. Phylogenic analysis indicates that T. congolense MSPs belong to five subfamilies that are conserved among African trypanosome species. Molecular modeling, based on the known structure of Leishmania Major GP63, 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 the T. congolense homologue TcoMSP-D (most closely related to Leishmania GP63). We detect TcoMSP-D in the serum of T. 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 with T. congolense significantly increases susceptibility to infection, indicating that immunity to TcoMSP-D is a factor affecting virulence.