Cyclic AMP signalling and glucose metabolism mediate pH taxis by African trypanosomes
Autor: | Shaw, Sebastian, Knüsel, Sebastian, Abbühl, Daniel, Naguleswaran, Arunasalam, Etzensperger, Ruth, Benninger, Mattias, Roditi, Isabel |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
Trypanosoma
Insecta media_common.quotation_subject Science Protozoan Proteins Adenylate kinase Insect Carbohydrate metabolism Cyclase Article Cyclic AMP Animals Taxis Response media_common biology Chemistry Tartrate-Resistant Acid Phosphatase Chemotaxis fungi Tsetse fly Phosphodiesterase Midgut Hydrogen-Ion Concentration biology.organism_classification Cell biology Parasite biology Glucose 3' 5'-Cyclic-AMP Phosphodiesterases Carbohydrate Metabolism Digestive System Cell signalling Signal Transduction |
Zdroj: | Nature Communications, Vol 13, Iss 1, Pp 1-13 (2022) Nature Communications |
ISSN: | 2041-1723 |
Popis: | The collective movement of African trypanosomes on semi-solid surfaces, known as social motility, is presumed to be due to migration factors and repellents released by the parasites. Here we show that procyclic (insect midgut) forms acidify their environment as a consequence of glucose metabolism, generating pH gradients by diffusion. Early and late procyclic forms exhibit self-organising properties on agarose plates. While early procyclic forms are repelled by acid and migrate outwards, late procyclic forms remain at the inoculation site. Furthermore, trypanosomes respond to exogenously formed pH gradients, with both early and late procyclic forms being attracted to alkali. pH taxis is mediated by multiple cyclic AMP effectors: deletion of one copy of adenylate cyclase ACP5, or both copies of the cyclic AMP response protein CARP3, abrogates the response to acid, while deletion of phosphodiesterase PDEB1 completely abolishes pH taxis. The ability to sense pH is biologically relevant as trypanosomes experience large changes as they migrate through their tsetse host. Supporting this, a CARP3 null mutant is severely compromised in its ability to establish infections in flies. Based on these findings, we propose that the expanded family of adenylate cyclases in trypanosomes might govern other chemotactic responses in their two hosts. African trypanosomes collectively move in a process called social motility. Here, the authors show that procyclic forms acidify their environment as a consequence of glucose metabolism, generating pH gradients by diffusion that are sensed via cyclic AMP signalling. Parasite mutants defective in cAMP signaling are inhibited in fly infection. |
Databáze: | OpenAIRE |
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