Flagellar cAMP signaling controls trypanosome progression through host tissues

• Published in: Nature communications 2019-02, Vol.10 (1), p.803-803, Article 803
• Main Authors: Shaw, Sebastian, DeMarco, Stephanie F., Rehmann, Ruth, Wenzler, Tanja, Florini, Francesca, Roditi, Isabel, Hill, Kent L.
• Format: Article
• Language: English
• Subjects: 13; 14; 14/19; 14/34; 14/35; 14/63; 3',5'-Cyclic-AMP Phosphodiesterases - genetics; 3',5'-Cyclic-AMP Phosphodiesterases - metabolism; 45; 59; 631/326/417/1716; 631/80/84/2334; 631/80/86; 64; 692/699/255/1715; 96; 96/95; Animals; Cell migration; Chemotaxis; Confocal microscopy; Cyclic AMP; Cyclic AMP - metabolism; Digestive System - parasitology; Flagella; Flagella - metabolism; Flies; Fluorescence; Gene Knockout Techniques; Host-Parasite Interactions; Humanities and Social Sciences; Insects; Microscopy; Midgut; multidisciplinary; Muscidae; Mutants; Mutation; Parasites; Phosphodiesterase; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Science; Science (multidisciplinary); Signal Transduction; Signaling; Tissues; Trypanosoma brucei brucei - metabolism; Trypanosoma brucei brucei - pathogenicity; Trypanosome; Trypanosomiasis, African - veterinary; Tsetse Flies - parasitology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-08696-y

The unicellular parasite Trypanosoma brucei is transmitted between mammals by tsetse flies. Following the discovery that flagellar phosphodiesterase PDEB1 is required for trypanosomes to move in response to signals in vitro (social motility), we investigated its role in tsetse flies. Here we show that PDEB1 knockout parasites exhibit subtle changes in movement, reminiscent of bacterial chemotaxis mutants. Infecting flies with the knockout, followed by live confocal microscopy of fluorescent parasites within dual-labelled insect tissues, shows that PDEB1 is important for traversal of the peritrophic matrix, which separates the midgut lumen from the ectoperitrophic space. Without PDEB1, parasites are trapped in the lumen and cannot progress through the cycle. This demonstrates that the peritrophic matrix is a barrier that must be actively overcome and that the parasite’s flagellar cAMP signaling pathway facilitates this. Migration may depend on perception of chemotactic cues, which could stem from co-infecting parasites and/or the insect host. Trypanosoma brucei probably relies on chemotactic signals for movement through tsetse fly tissues, but the molecular basis is unknown. Here, the authors show that flagellar cAMP signaling is required for traversal of the peritrophic matrix and that, without it, parasites are trapped in the midgut lumen.