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Carbohydrate-binding agents act as potent trypanocidals that elicit modifications in VSG glycosylation and reduced virulence in Trypanosoma brucei

Victor M Castillo-Acosta, Antonio E Vidal, Luis M Ruiz-Pérez, Els Van Damme UGent, Yasuhiro Igarashi, Jan Balzarini and Dolores González-Pacanowska (2013) MOLECULAR MICROBIOLOGY. 90(4). p.665-679
abstract
The surface of Trypanosoma brucei is covered by a dense coat of glycosylphosphatidylinositol-anchored glycoproteins. The major component is the variant surface glycoprotein (VSG) which is glycosylated by both paucimannose and oligomannose N-glycans. Surface glycans are poorly accessible and killing mediated by peptide lectin-VSG complexes is hindered by active endocytosis. However, contrary to previous observations, here we show that high-affinity carbohydrate binding agents bind to surface glycoproteins and abrogate growth of T.brucei bloodstream forms. Specifically, binding of the mannose-specific Hippeastrum hybrid agglutinin (HHA) resulted in profound perturbations in endocytosis and parasite lysis. Prolonged exposure to HHA led to the loss of triantennary oligomannose structures in surface glycoproteins as a result of genetic rearrangements that abolished expression of the oligosaccharyltransferase TbSTT3B gene and yielded novel chimeric enzymes. Mutant parasites exhibited markedly reduced infectivity thus demonstrating the importance of specific glycosylation patterns in parasite virulence.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
PLANT-LECTINS, URTICA-DIOICA, CELL-SURFACE, IN-VITRO, AFRICAN TRYPANOSOMES, GPI-ANCHORED PROTEINS, N-GLYCOSYLATION, BLOOD-STREAM FORM, HUMAN-IMMUNODEFICIENCY-VIRUS, VARIANT SURFACE GLYCOPROTEIN
journal title
MOLECULAR MICROBIOLOGY
Mol. Microbiol.
volume
90
issue
4
pages
665 - 679
Web of Science type
Article
Web of Science id
000330108000001
JCR category
MICROBIOLOGY
JCR impact factor
5.026 (2013)
JCR rank
19/119 (2013)
JCR quartile
1 (2013)
ISSN
0950-382X
DOI
10.1111/mmi.12359
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
4283483
handle
http://hdl.handle.net/1854/LU-4283483
date created
2014-02-07 18:28:53
date last changed
2016-12-19 15:46:07
@article{4283483,
  abstract     = {The surface of Trypanosoma brucei is covered by a dense coat of glycosylphosphatidylinositol-anchored glycoproteins. The major component is the variant surface glycoprotein (VSG) which is glycosylated by both paucimannose and oligomannose N-glycans. Surface glycans are poorly accessible and killing mediated by peptide lectin-VSG complexes is hindered by active endocytosis. However, contrary to previous observations, here we show that high-affinity carbohydrate binding agents bind to surface glycoproteins and abrogate growth of T.brucei bloodstream forms. Specifically, binding of the mannose-specific Hippeastrum hybrid agglutinin (HHA) resulted in profound perturbations in endocytosis and parasite lysis. Prolonged exposure to HHA led to the loss of triantennary oligomannose structures in surface glycoproteins as a result of genetic rearrangements that abolished expression of the oligosaccharyltransferase TbSTT3B gene and yielded novel chimeric enzymes. Mutant parasites exhibited markedly reduced infectivity thus demonstrating the importance of specific glycosylation patterns in parasite virulence.},
  author       = {Castillo-Acosta, Victor M and Vidal, Antonio E and Ruiz-P{\'e}rez, Luis M and Van Damme, Els and Igarashi, Yasuhiro and Balzarini, Jan and Gonz{\'a}lez-Pacanowska, Dolores},
  issn         = {0950-382X},
  journal      = {MOLECULAR MICROBIOLOGY},
  keyword      = {PLANT-LECTINS,URTICA-DIOICA,CELL-SURFACE,IN-VITRO,AFRICAN TRYPANOSOMES,GPI-ANCHORED PROTEINS,N-GLYCOSYLATION,BLOOD-STREAM FORM,HUMAN-IMMUNODEFICIENCY-VIRUS,VARIANT SURFACE GLYCOPROTEIN},
  language     = {eng},
  number       = {4},
  pages        = {665--679},
  title        = {Carbohydrate-binding agents act as potent trypanocidals that elicit modifications in VSG glycosylation and reduced virulence in Trypanosoma brucei},
  url          = {http://dx.doi.org/10.1111/mmi.12359},
  volume       = {90},
  year         = {2013},
}

Chicago
Castillo-Acosta, Victor M, Antonio E Vidal, Luis M Ruiz-Pérez, Els Van Damme, Yasuhiro Igarashi, Jan Balzarini, and Dolores González-Pacanowska. 2013. “Carbohydrate-binding Agents Act as Potent Trypanocidals That Elicit Modifications in VSG Glycosylation and Reduced Virulence in Trypanosoma Brucei.” Molecular Microbiology 90 (4): 665–679.
APA
Castillo-Acosta, V. M., Vidal, A. E., Ruiz-Pérez, L. M., Van Damme, E., Igarashi, Y., Balzarini, J., & González-Pacanowska, D. (2013). Carbohydrate-binding agents act as potent trypanocidals that elicit modifications in VSG glycosylation and reduced virulence in Trypanosoma brucei. MOLECULAR MICROBIOLOGY, 90(4), 665–679.
Vancouver
1.
Castillo-Acosta VM, Vidal AE, Ruiz-Pérez LM, Van Damme E, Igarashi Y, Balzarini J, et al. Carbohydrate-binding agents act as potent trypanocidals that elicit modifications in VSG glycosylation and reduced virulence in Trypanosoma brucei. MOLECULAR MICROBIOLOGY. 2013;90(4):665–79.
MLA
Castillo-Acosta, Victor M, Antonio E Vidal, Luis M Ruiz-Pérez, et al. “Carbohydrate-binding Agents Act as Potent Trypanocidals That Elicit Modifications in VSG Glycosylation and Reduced Virulence in Trypanosoma Brucei.” MOLECULAR MICROBIOLOGY 90.4 (2013): 665–679. Print.