The Flagellar Arginine Kinase in Trypanosoma brucei Is Important for Infection in Tsetse Flies.

Cher-Pheng Ooi,Daria Julkowska,Ines Subota,Brice Rotureau,Thierry Blisnick,Christina Georgikou,Philippe Bastin,Simonetta Gribaldo,Sylvie Perrot,Frank Voncken

doi:10.1371/journal.pone.0133676

Cher-Pheng Ooi, Daria Julkowska + Show 8 more

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https://doi.org/10.1371/journal.pone.0133676

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Abstract

African trypanosomes are flagellated parasites that cause sleeping sickness. Parasites are transmitted from one mammalian host to another by the bite of a tsetse fly. Trypanosoma brucei possesses three different genes for arginine kinase (AK) including one (AK3) that encodes a protein localised to the flagellum. AK3 is characterised by the presence of a unique amino-terminal insertion that specifies flagellar targeting. We show here a phylogenetic analysis revealing that flagellar AK arose in two independent duplication events in T. brucei and T. congolense, the two species of African trypanosomes that infect the tsetse midgut. In T. brucei, AK3 is detected in all stages of parasite development in the fly (in the midgut and in the salivary glands) as well as in bloodstream cells, but with predominance at insect stages. Genetic knockout leads to a slight reduction in motility and impairs parasite infectivity towards tsetse flies in single and competition experiments, both phenotypes being reverted upon expression of an epitope-tagged version of AK3. We speculate that this flagellar arginine kinase is important for T. brucei infection of tsetse, especially in the context of mixed infections and that its flagellar targeting relies on a system equivalent to that discovered for calflagins, a family of trypanosome flagellum calcium binding proteins.

Highlights

Trypanosomes are the causative parasites of human African trypanosomiasis, called sleeping sickness
We present phylogenetic data revealing that trypanosome arginine kinase (AK) genes were likely acquired by horizontal gene transfer from an invertebrate host and that separate duplication events led to the emergence of flagellar forms of AK in T. brucei and possibly in T. congolense, the two species that undergo the most exhaustive development in the tsetse fly
The first report for AK in trypanosomatids was published by Pereira and coworkers who cloned an AK gene from Trypanosoma cruzi, highlighting the remarkable conservation of the core protein that shows ~70% identity with various insect or crustacean AK [33]

Summary

Introduction

Trypanosomes are the causative parasites of human African trypanosomiasis, called sleeping sickness. On the decline [1,2], the human and animal forms of the disease still constitute a major health and economic burden on the African continent. Transmission of the parasite relies almost exclusively on the infective bite of the tsetse fly (Glossina sp.). Understanding the factors that allow for the successful infection of the insect vector remains a relevant research interest. The fly is more than a passive vector as the parasites undergo specific development programmes before becoming infective again. These can be relatively simple as in PLOS ONE | DOI:10.1371/journal.pone.0133676. These can be relatively simple as in PLOS ONE | DOI:10.1371/journal.pone.0133676 July 28, 2015

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