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Characterization of major surface protease homologues of Trypanosoma congolense

Veronica Marcoux1, Guojian Wei, Henry Tabel

  • 1Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.

Journal of Biomedicine & Biotechnology
|February 11, 2010
PubMed

Insights

African trypanosome Major Surface Metalloproteases (MSPs) show subfamily-specific structures, suggesting distinct functions. Immunity to one T. congolense MSP surprisingly increased infection susceptibility, revealing a role in virulence.

Area of Science:

  • Parasitology
  • Structural Biology
  • Immunology

Background:

  • Trypanosomes possess Major Surface Metalloproteases (MSPs) crucial for their lifecycle.
  • Six putative MSPs have been identified in the Trypanosoma congolense genome.
  • Phylogenetic analysis reveals conserved MSP subfamilies across African trypanosomes.

Purpose of the Study:

  • To investigate the structural diversity and functional implications of T. congolense MSPs.
  • To characterize the T. congolense homologue TcoMSP-D and its immune response.
  • To determine the role of TcoMSP-D immunity in T. congolense infection virulence.

Main Methods:

  • Phylogenetic analysis of T. congolense MSPs.
  • Molecular modeling of MSP structures based on Leishmania GP63.
  • Cloning, purification, and immunization using the TcoMSP-D amino-terminal domain.
  • Detection of TcoMSP-D in infected mouse serum.
  • Assessing infection susceptibility in immunized mice.

Main Results:

  • T. congolense MSPs fall into five conserved subfamilies with subfamily-specific structural variations near the active site.
  • TcoMSP-D was detected in the serum of infected mice.
  • Immunization with TcoMSP-D induced a sustained IgG1 antibody response.
  • Mice immunized with TcoMSP-D showed increased susceptibility to T. congolense infection.

Conclusions:

  • MSP subfamilies in T. congolense likely recognize distinct substrates due to structural variations.
  • TcoMSP-D is present during infection and elicits an antibody response.
  • Immunity to TcoMSP-D paradoxically enhances T. congolense virulence, suggesting a complex role in host-parasite interactions.

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