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The human trypanolytic factor: a drug shaped naturally
1Laboratory of Molecular Parasitology and Laboratory of Molecular Biology of Ectoparasites, IBMM (Institute for Molecular Biology and Medicine), Université Libre de Bruxelles, 12 rue des Professeurs Jeener et Brachet,6041 Gosselies, Belgium. luvhamme@ulb.ac.be
Infectious Disorders Drug Targets
|May 1, 2010
Summary
African trypanosomes cause devastating diseases. A specific serum particle protects humans, but some trypanosome species evolved resistance, offering insights into host-pathogen evolution and potential drug targets.
Area of Science:
- Parasitology
- Immunology
- Evolutionary Biology
Background:
- African trypanosomes cause human sleeping sickness and cattle nagana, significant health burdens in Africa.
- Most trypanosome species are lysed by human serum via a specific particle (HDL subclass) containing apolipoprotein L1 and haptoglobin related protein.
- Two species, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, infect humans by resisting this serum-mediated lysis.
Purpose of the Study:
- To review the mechanisms of serum lysis and resistance in African trypanosomes.
- To examine the molecular components and modes of action involved in this host-pathogen interaction.
- To explore the potential of this system as a source for novel drug targets and synthetic drugs.
Main Methods:
- Review of existing literature on trypanolysis and resistance mechanisms.
- Analysis of the molecular components, including apolipoprotein L1 and haptoglobin related protein.
- Discussion of the evolutionary arms race between pathogen and host.
Main Results:
- Serum resistance in Trypanosoma brucei rhodesiense is mediated by a single gene, SRA.
- The lysis-resistance mechanism represents a natural drug-antidote system.
- The identified molecular components and their interactions are key to understanding this system.
Conclusions:
- The trypanolysis and resistance system provides a model for pathogen-host co-evolution.
- Components of this system are potential targets for developing new drugs against sleeping sickness.
- Engineering this natural system could lead to the creation of effective synthetic drugs.
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