Human serum resistance in African trypanosome

Parasites are the most amazing living organisms. An example of a successful parasite is Trypanosoma brucei. I am particularly interested in the subspecies T. b. brucei, causing Nagana in ungulates, and T. b. rhodesiense, causing sleeping sickness in humans. Upon encounter with human serum, which contains trypanosome lytic factor (TLF), T. b. brucei is lysed and thus unable to establish human infection. The human pathogen T. b. rhodesiense evolved to overcome this lytic activity. It is currently believed that expression of the serum resistance associated gene (SRA) correlates to human serum resistance in T. b. rhodesiense. The mechanism of resistance is not understood.;The questions in this dissertation addresses the mechanism of serum resistance in human infective trypanosomes. I transfected epitope tagged SRA into serum sensitive T. b. brucei cells. This allowed me to determine the subcellular localization of SRA protein and I found that SRA and TLF colocalize in subcellular vesicles.;I was also interested in the evolution of serum resistance. To mimic the evolution of serum resistance in vitro, we gradually increased the TLF concentration in the growth media of T. b. brucei. After 9 mo, we obtained a serum resistant variant. Since SRA is not present in these organisms, other resistance factors must exist. A putative serum resistance gene, the serum resistance associated gene homologue (SRH), was shown not to be involved in mediating serum resistance in these cells. It is possible that a newly expressed variable surface glycoprotein (VSG) is involved in mediating resistance. The examination of these T. b. brucei variants will aid in the understanding of alternative mechanisms of serum resistance.;As with all results obtained, more questions become apparent. I am leaving this project at a very exciting point. For the first time we are able to combine the TLF and the SRA project. How does SRA interact with TLF? I am sure that over the next years, this assignment will be fruitful and will provide many answers to the old and intriguing questions of serum lysis and serum resistance in African trypanosomes.