Trypanosoma brucei
(from Dr. Torsten Ochsenreiter)
Working model: Why Trypanosomes ?
Trypanosomatids (including Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp.) are unicellular protozoan parasites among which several species are responsible for disease known as “the most neglected”, although they affect ~24 million people all over the world (ref). Sleeping sickness (causative agent: T. brucei) is a fatal disease if untreated. However, there is no vaccine, existing medications have severe side effects (including death) and drug resistance is increasing dramatically. Similar problems are encountered for Chagas disease (T. cruzi) and leishmaniasis (Leishmania spp.).
Other trypanosomatid species cause diseases affecting domestic animals (African trypanosomes: T. congolense, T. vivax, T. evansi, etc) and are thus, in addition to human health problems, responsible for very serious additional economical problems in developing countries. New anti-trypanosomatid treatments (drug and/or vaccine) need to be developed, since the therapeutic arsenal remains limited against both the Human and domestic animal diseases.
Trypanosomes are also famous for a variety of very unusual genetic and biochemical features, that stimulate broad scientific and evolutionary interest. These include exotic mechanisms of gene expression like polycistronic transcription of genes (ref), maturation of pre-messenger RNA by trans-splicing (ref), extensive editing of mitochondrial RNAs (ref), sophisticated mechanisms of immune evasion like antigenic variation (ref), antibody endocytosis (ref), compartmentalisation of glycolysis in glycosomes, which are peroxisome-like organelles (ref), unusual pathways for de novo synthesis of fatty acids (ref), etc.
Trypanosomatid species are amenable to gene knockout, with 5 available selectable markers. In addition, another very powerful reverse genetic tool (RNAi) has been developed in T. brucei to specifically inhibit the expression of a target gene (ref). However, this tool failed to be functional in T. cruzi (ref) and Leishmania spp. (ref). Consequently, both the mammalian (bloodstream form) and insect (procyclic form) stages of T. brucei have become the favourite models to study metabolism and other processes shared with other trypanosomatid species.