Chemotactic responses of Trypanosoma brucei procyclic forms to proline and other metabolites

Many protozoan parasites have complex life cycles entailing migration through different organs in their hosts, but the cues guiding them remain poorly understood. Using a semi-solid plate motility assay, we show that early procyclic forms of Trypanosoma brucei, the first stage to develop in the tsetse fly midgut, perceive several metabolites - including glucose, glycerol and proline - as chemoattractants, while the glycolytic end-product succinate acts as a repellent. During adaptation in the fly, T. brucei switches from glucose/glycerol to proline as its primary energy source. We show that the parasite's chemotactic response towards proline requires adenylate cyclase ACP5 and the cyclic AMP response protein CARP3, two components of a signalling pathway involved in pH sensing. These results are consistent with a role for T. brucei's expanded repertoire of adenylate cyclases as environmental sensors, providing a tractable system for future studies on how trypanosomes navigate through the host.