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bioRxiv · 10.64898/2026.07.02.736028

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

Knüsel, S.·Benninger, M.·Versluis, D. M.·Insall, R.·Tiengwe, C.·Roditi, I.
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Abstract

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 parasites chemotactic response towards proline requires adenylate cyclase ACP5 and the cyclic AMP response protein CARP3, two components of signalling pathway involved in pH sensing. These results further support a role for T. bruceis expanded repertoire of receptor adenylate cyclases as environmental sensors that guide navigation through the host. HighlightsO_LIThe plate assay reported here can be used to study how trypanosomes sense external signals and migrate in response to them. C_LIO_LIEarly procyclic forms of T. brucei respond to a variety of metabolites and exhibit different patterns of collective migration on plates, depending on the stimulus. C_LIO_LIThe response to proline operates through cAMP signalling and requires ACP5 and CARP3, two components also required for pH sensing. C_LI

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Knüsel, S., Benninger, M., Versluis, D. M., Insall, R., Tiengwe, C., Roditi, I.. 2026-07-03. Chemotactic responses of Trypanosoma brucei procyclic forms to proline and other metabolites. https://doi.org/10.64898/2026.07.02.736028

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