Survival in and colonization of the tsetse fly midgut are essential steps in the transmission of many species of African trypanosomes. In the fly, bloodstream trypanosomes transform into the procyclic stage within the gut lumen and later migrate to the ectoperitrophic space, where they multiply, establishing an infection. Progression of the parasite infection in the fly depends on factors inherent to the biology of trypanosomes, tsetse, and the bloodmeal. Flies usually eradicate infection early on with both pre-existing and inducible factors. Parasites, in contrast, respond to these stimuli by undergoing developmental changes, allowing a few to both survive and migrate within the tsetse. Here we discuss parasite and fly factors determining trypanosome colonization of the tsetse, focusing mainly on the midgut.
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