|dc.description.abstract||The protozoan parasites Trypanosoma brucei brucei, Trypanosoma congolense and
Trypanosoma vivax cause Animal African Trypanosomiasis, a disease responsible
for costly livestock pathology and economic losses in Africa. Each of these African
trypanosomes are vector-borne and transmitted by the blood-feeding tsetse fly.
Additional blood-feeding vectors can spread T. vivax, extending its range into South
T. b. brucei infection of the mammalian host progresses in waves, with periodic
clearance of antigenic variants. Accumulation of slender parasites in the blood is
accompanied by accumulation of the density-sensing factor, SIF (stumpy induction
factor). SIF drives differentiation from the proliferative slender form to the growth
arrested stumpy form at the peak of parasitaemia. This differentiation step aids host
survival, and the stumpy form is pre-adapted for continuation of development in the
tsetse fly, ensuring transmissibility.
Despite facing challenges comparable to T. b. brucei during their life cycle, T.
congolense and T. vivax are not found to have morphologically distinguishable
slender and stumpy forms. The growth control mechanisms used by these important
veterinary pathogens have been investigated in this thesis. Particular focus has been
placed on the conservation of quorum sensing pathways within the African
Trypanosomes. The potential for cross-species communication has implications for
T. congolense was found to undergo growth arrest at peak parasitaemia, and
transcriptomic changes occurring between ascending and peak parasitaemia were
identified and comparisons made to T. b. brucei slender and stumpy transcriptomes.
In an examination of the conservation of the SIF-responsive pathway, expression of a
T. congolense orthologue was found to rescue stumpy formation in an otherwise SIF-resistant
null mutant for the corresponding T. b. brucei gene.
The capacity for cross-talk between density-sensing signals in different trypanosome
species was tested using conditioned medium from T. congolense bloodstream form
cultures. This could activate the expression of a stumpy specific reporter protein in T.
b. brucei. A cell line deficient in a SIF-responsive gene showed resistance to the
conditioned medium with a delay in reporter expression.
These results highlight the unanticipated capacity for different trypanosome species
to exhibit intra and inter specific cell-cell communication in the mammalian
bloodstream, with possible consequences for their virulence, transmission and