Publication Date:
2009-05-16
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685892/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dean, Samuel -- Marchetti, Rosa -- Kirk, Kiaran -- Matthews, Keith R -- 073358/Wellcome Trust/United Kingdom -- 082555/Wellcome Trust/United Kingdom -- BB/E012442/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 May 14;459(7244):213-7. doi: 10.1038/nature07997.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444208" target="_blank"〉PubMed〈/a〉
Keywords:
Aconitic Acid/analogs & derivatives/metabolism
;
Animals
;
Cell Differentiation
;
Citric Acid/metabolism
;
Gene Expression Regulation, Developmental
;
Insect Vectors/parasitology
;
Oocytes
;
Protozoan Proteins/genetics/*metabolism
;
RNA Interference
;
RNA, Messenger/genetics/metabolism
;
RNA, Protozoan/genetics/metabolism
;
Temperature
;
Trypanosoma brucei brucei/cytology/genetics/*growth & development/*metabolism
;
Trypanosomiasis, African/parasitology
;
Tsetse Flies/parasitology
;
Xenopus laevis
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
