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A surface transporter family conveys the trypanosome differentiation signal

Date

2009

Authors

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

Journal Title

Journal ISSN

Volume Title

Publisher

Macmillan Publishers Ltd

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.

Description

Keywords

Keywords: aconitic acid; citric acid; cold shock protein; blood; disease vector; environmental cue; fly; gene expression; host-parasite interaction; host-pathogen interaction; life cycle; low temperature; mammal; molecular analysis; parasitic disease; protein; prot

Citation

Source

Nature

Type

Journal article

Book Title

Entity type

Access Statement

License Rights

DOI

10.1038/nature07997

Restricted until

2037-12-31