Basic Biology of Trypanosoma brucei with reference to the development of chemotherapies

Abstract

: Trypanosoma brucei are protozoan parasites that causes the lethal human disease African sleeping sickness, and the economically devastating disease of cattle, Nagana. African sleeping sickness, or Human African Trypanosomiasis (HAT) threatens 65 million people, and animal trypanosomiasis makes large areas of farmland unusable. There is no vaccine and licenced therapies against the most severe, late-stage disease are toxic, impractical and ineffective. Trypanosomes are transmitted by tsetse flies and HAT is therefore predominantly confined to the tsetse fly belt in subSaharan African. They are exclusively extracellular, and they differentiate between at least seven developmental forms that are highly adapted to host and vector niches. In the mammalian (human) host they inhabit the blood, cerebrospinal fluid (late stage disease), skin and adipose fat. In the tsetse fly vector, they travel from the tsetse midgut to the salivary glands via the ectoperitrophic space and proventriculus. Trypanosomes are evolutionarily divergent compared with most branches of eukaryotic life. Perhaps most famous for their extraordinary mechanisms of monoallelic gene expression and antigenic variation, they have also been investigated because much of their biology is either highly unconventional or extreme. Moreover, in addition to their importance as pathogens, many researchers have been attracted to the field because trypanosomes have some of the most advanced molecular genetic tools and database resources of any model system. The following will cover just some aspects of trypanosome biology and how its divergent biochemistry has been leveraged to develop drugs to treat African Sleeping sickness. It is by no means intended to be a comprehensive survey of trypanosome features. Rather, it is hoped that it will present trypanosomes as one of the most fascinating and tractable systems in which to do discovery biology.