Exposure of Trypanosoma brucei to an N-acetylglucosamine-binding lectin induces VSG switching and glycosylation defects resulting in reduced infectivity

PLoS Neglected Tropical Diseases
Víctor M Castillo-AcostaDolores González-Pacanowska

Abstract

Trypanosoma brucei variant surface glycoproteins (VSG) are glycosylated by both paucimannose and oligomannose structures which are involved in the formation of a protective barrier against the immune system. Here, we report that the stinging nettle lectin (UDA), with predominant N-acetylglucosamine-binding specificity, interacts with glycosylated VSGs and kills parasites by provoking defects in endocytosis together with impaired cytokinesis. Prolonged exposure to UDA induced parasite resistance based on a diminished capacity to bind the lectin due to an enrichment of biantennary paucimannose and a reduction of triantennary oligomannose structures. Two molecular mechanisms involved in resistance were identified: VSG switching and modifications in N-glycan composition. Glycosylation defects were correlated with the down-regulation of the TbSTT3A and/or TbSTT3B genes (coding for oligosaccharyltransferases A and B, respectively) responsible for glycan specificity. Furthermore, UDA-resistant trypanosomes exhibited severely impaired infectivity indicating that the resistant phenotype entails a substantial fitness cost. The results obtained further support the modification of surface glycan composition resulting from down-regulation o...Continue Reading

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Citations

Sep 21, 2017·The Journal of Biological Chemistry·Anders JinnelovMichael A J Ferguson
Jul 28, 2018·Journal of Applied Microbiology·L C Breitenbach Barroso CoelhoM T Dos Santos Correia
Sep 24, 2016·PLoS Pathogens·Víctor M Castillo-AcostaDolores González-Pacanowska
Aug 15, 2019·Biological Reviews of the Cambridge Philosophical Society·Harry C TjondroMorten Thaysen-Andersen
Jun 16, 2021·Carbohydrate Research·Dixita ChettriAnil Kumar Verma

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Methods Mentioned

BETA
PCR
flow cytometry
glycosylation
electrophoresis
fluorescence 3D microscopy
FACS
fluorescence microscopy

Software Mentioned

Huygens Essential
BD CellQuest Pro
Cell R IX81
GraphPad
Image J

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