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

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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 of the genes coding for oligosaccharyltransferases as a general resistance mechanism in response to prolonged exposure to carbohydrate-binding agents.
Keywords
AFRICAN TRYPANOSOMES, IN-VITRO, ENDOCYTOSIS, PROTEIN, MANNOSE, CELL-SURFACE, LINKED OLIGOSACCHARIDES, URTICA-DIOICA AGGLUTININ, VARIANT SURFACE GLYCOPROTEIN, BLOOD-STREAM FORM

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Chicago
Castillo-Acosta, Victor M, Luis M Ruiz-Perez, Els Van Damme, Jan Balzarini, and Dolores Gonzalez-Pacanowska. 2015. “Exposure of Trypanosoma Brucei to an N-acetylglucosamine-binding Lectin Induces VSG Switching and Glycosylation Defects Resulting in Reduced Infectivity.” Plos Neglected Tropical Diseases 9 (3).
APA
Castillo-Acosta, V. M., Ruiz-Perez, L. M., Van Damme, E., Balzarini, J., & Gonzalez-Pacanowska, D. (2015). Exposure of Trypanosoma brucei to an N-acetylglucosamine-binding lectin induces VSG switching and glycosylation defects resulting in reduced infectivity. PLOS NEGLECTED TROPICAL DISEASES, 9(3).
Vancouver
1.
Castillo-Acosta VM, Ruiz-Perez LM, Van Damme E, Balzarini J, Gonzalez-Pacanowska D. Exposure of Trypanosoma brucei to an N-acetylglucosamine-binding lectin induces VSG switching and glycosylation defects resulting in reduced infectivity. PLOS NEGLECTED TROPICAL DISEASES. 2015;9(3).
MLA
Castillo-Acosta, Victor M, Luis M Ruiz-Perez, Els Van Damme, et al. “Exposure of Trypanosoma Brucei to an N-acetylglucosamine-binding Lectin Induces VSG Switching and Glycosylation Defects Resulting in Reduced Infectivity.” PLOS NEGLECTED TROPICAL DISEASES 9.3 (2015): n. pag. Print.
@article{5976318,
  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 of the genes coding for oligosaccharyltransferases as a general resistance mechanism in response to prolonged exposure to carbohydrate-binding agents.},
  articleno    = {e0003612},
  author       = {Castillo-Acosta, Victor M and Ruiz-Perez, Luis M and Van Damme, Els and Balzarini, Jan and Gonzalez-Pacanowska, Dolores},
  issn         = {1935-2735},
  journal      = {PLOS NEGLECTED TROPICAL DISEASES},
  keyword      = {AFRICAN TRYPANOSOMES,IN-VITRO,ENDOCYTOSIS,PROTEIN,MANNOSE,CELL-SURFACE,LINKED OLIGOSACCHARIDES,URTICA-DIOICA AGGLUTININ,VARIANT SURFACE GLYCOPROTEIN,BLOOD-STREAM FORM},
  language     = {eng},
  number       = {3},
  pages        = {21},
  title        = {Exposure of Trypanosoma brucei to an N-acetylglucosamine-binding lectin induces VSG switching and glycosylation defects resulting in reduced infectivity},
  url          = {http://dx.doi.org/10.1371/journal.pntd.0003612},
  volume       = {9},
  year         = {2015},
}

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