Oxidative phosphorylation is required for powering motility and development of the sleeping sickness parasite Trypanosoma brucei in the tsetse fly vector

Caroline Dewar, Aitor Casas-Sánchez, Constentin Dieme, Aline Crouzols, Lee R Haines, Álvaro Acosta-Serrano, Brice Rotureau, Achim Schnaufer

Research output: Contribution to journalArticlepeer-review

Abstract

The single-celled parasite Trypanosoma brucei is transmitted by hematophagous tsetse flies. Lifecycle progression from mammalian bloodstream form to tsetse midgut form and, subsequently, infective salivary gland form depends on complex developmental steps and migration within different fly tissues. As the parasite colonises the glucose-poor insect midgut, ATP production is thought to depend on activation of mitochondrial amino acid catabolism via oxidative phosphorylation (OXPHOS). This process involves respiratory chain complexes and F1FO-ATP synthase and requires protein subunits of these complexes that are encoded in the parasite's mitochondrial DNA (kDNA). Here we show that progressive loss of kDNA-encoded functions correlates with a decreasing ability to initiate and complete development in the tsetse. First, parasites with a mutated F1FO-ATP synthase with reduced capacity for OXPHOS can initiate differentiation from bloodstream to insect form, but they are unable to proliferate in vitro. Unexpectedly, these cells can still colonise the tsetse midgut. However, these parasites exhibit a motility defect and are severely impaired in colonising or migrating to subsequent tsetse tissues. Second, parasites with a fully disrupted F1FO-ATP synthase complex that is completely unable to produce ATP by OXPHOS can still differentiate to the first insect stage in vitro but die within a few days and cannot establish a midgut infection in vivo. Third, parasites lacking kDNA entirely can initiate differentiation but die soon after. Together, these scenarios suggest that efficient ATP production via OXPHOS is not essential for initial colonisation of the tsetse vector but is required to power trypanosome migration within the fly.
Original languageEnglish
Article numbere02357-21
Number of pages24
JournalmBio
Volume13
Issue number1
DOIs
Publication statusPublished - 11 Jan 2022

Keywords

  • ATP synthase
  • Trypanosoma brucei
  • human African trypanosomiasis
  • mitochondria
  • mitochondrial metabolism
  • oxidative phosphorylation
  • sleeping sickness
  • trypanosomes
  • tsetse fly

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