Trypanosoma brucei are protozoan parasites that cause the lethal human disease African sleeping
sickness and the economically devastating disease of cattle, Nagana. African sleeping sickness, also known as
Human African Trypanosomiasis (HAT), threatens 65 million people and animal trypanosomiasis makes large
areas of farmland unusable. There is no vaccine and licensed 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 sub-Saharan Africa. 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. This is by no means intended
to be a comprehensive survey of trypanosome features. Rather, I hope to present trypanosomes as one of the
most fascinating and tractable systems to do discovery biology.
Keywords: Trypanosoma brucei, trypanosome, kinetoplastid, parasite, African sleeping sickness, trypanosomiasis, chemotherapy, cell biology,
life cycle, tsetse fly.
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