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

PLoS One. 2015 Jul 28;10(7):e0133676. doi: 10.1371/journal.pone.0133676. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Kinase / genetics
  • Arginine Kinase / metabolism*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Flagella / genetics
  • Flagella / metabolism
  • Life Cycle Stages / physiology*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Trypanosoma brucei brucei / enzymology*
  • Tsetse Flies / parasitology*

Substances

  • Calcium-Binding Proteins
  • Protozoan Proteins
  • Arginine Kinase

Grants and funding

This work was funded by the Institut Pasteur and by the Centre National de la Recherche Scientifique (CNRS). CPO was funded by a DIM Ile-de-France postdoctoral fellowship (DIM-MALINF-110071) and by a French Government Investissement d’Avenir programme, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID). IS was funded by a Fonds National de la Recherche du Luxembourg (TR-PHD BFR 07-023) fellowship and DJ by a Roux post-doctoral fellowship (Institut Pasteur). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.