A surface transporter family conveys the trypanosome differentiation signal

Samuel Dean*, Rosa Marchetti, Kiaran Kirk, Keith R. Matthews

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    175 Citations (Scopus)

    Abstract

    Microbial pathogens use environmental cues to trigger the developmental events needed to infect mammalian hosts or transmit to disease vectors. The parasites causing African sleeping sickness respond to citrate or cis-aconitate (CCA) to initiate life-cycle development when transmitted to their tsetse fly vector. This requires hypersensitization of the parasites to CCA by exposure to low temperature, conditions encountered after tsetse fly feeding at dusk or dawn. Here we identify a carboxylate-transporter family, PAD (proteins associated with differentiation), required for perception of this differentiation signal. Consistent with predictions for the response of trypanosomes to CCA, PAD proteins are expressed on the surface of the transmission-competent stumpy-form parasites in the bloodstream, and at least one member is thermoregulated, showing elevated expression and surface access at low temperature. Moreover, RNA-interference-mediated ablation of PAD expression diminishes CCA-induced differentiation and eliminates CCA hypersensitivity under cold-shock conditions. As well as being molecular transducers of the differentiation signal in these parasites, PAD proteins provide the first example of a surface marker able to discriminate the transmission stage of trypanosomes in their mammalian host.

    Original languageEnglish
    Pages (from-to)213-217
    Number of pages5
    JournalNature
    Volume459
    Issue number7244
    DOIs
    Publication statusPublished - 14 May 2009

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