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Novel regulators of social motility in the African trypanosome, Trypanosoma brucei


Trypanosoma brucei is the causative agent of sleeping sickness, a major threat to economic stability and public health across sub-Saharan Africa. This protozoan parasite features a complex digenetic life cycle that alternates between the tsetse fly (Glossina spp.) vector and the mammalian host. Infections in both the fly and vector are characterized by intimate contact with tissue surfaces. Recent studies have shown that when cultivated on semisolid agarose surfaces, T. brucei engages in social behavior, termed social motility, which manifests as parasites assembling into groups that move collectively to form symmetrical arrays of radial projections. Herein we describe two novel modulators of social motility in T. brucei, the zinc finger protein ZC3H34 and the prolyl isomerase cyclophilin A (CyPA). Using RNA interference, we show that knockdown of either ZC3H34 or CyPA delays social motility. The delay in social motility observed with CyPA knockdown is not due to decreased propulsive motility, although ZC3H34-depleted parasites do show reduced propulsive motility. Our study provides new insights into the biochemistry of trypanosome social behavior and identifies potential targets for chemical inhibition of vector-to-host parasite transmission.

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