Tsetse salivary glycoproteins are modified with paucimannosidic N-glycans, are recognised by C-type lectins and bind to trypanosomes

PLoS Negl Trop Dis. 2021 Feb 2;15(2):e0009071. doi: 10.1371/journal.pntd.0009071. eCollection 2021 Feb.

Abstract

African sleeping sickness is caused by Trypanosoma brucei, a parasite transmitted by the bite of a tsetse fly. Trypanosome infection induces a severe transcriptional downregulation of tsetse genes encoding for salivary proteins, which reduces its anti-hemostatic and anti-clotting properties. To better understand trypanosome transmission and the possible role of glycans in insect bloodfeeding, we characterized the N-glycome of tsetse saliva glycoproteins. Tsetse salivary N-glycans were enzymatically released, tagged with either 2-aminobenzamide (2-AB) or procainamide, and analyzed by HILIC-UHPLC-FLR coupled online with positive-ion ESI-LC-MS/MS. We found that the N-glycan profiles of T. brucei-infected and naïve tsetse salivary glycoproteins are almost identical, consisting mainly (>50%) of highly processed Man3GlcNAc2 in addition to several other paucimannose, high mannose, and few hybrid-type N-glycans. In overlay assays, these sugars were differentially recognized by the mannose receptor and DC-SIGN C-type lectins. We also show that salivary glycoproteins bind strongly to the surface of transmissible metacyclic trypanosomes. We suggest that although the repertoire of tsetse salivary N-glycans does not change during a trypanosome infection, the interactions with mannosylated glycoproteins may influence parasite transmission into the vertebrate host.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, Liquid
  • Concanavalin A
  • Glycoproteins / metabolism*
  • Glycoside Hydrolases
  • Insect Vectors / parasitology
  • Lectins, C-Type / metabolism*
  • Polysaccharides / metabolism*
  • Saliva
  • Salivary Glands / parasitology
  • Salivary Proteins and Peptides / metabolism*
  • Tandem Mass Spectrometry
  • Trypanosoma / metabolism*
  • Trypanosoma brucei brucei / genetics
  • Trypanosomiasis, African / parasitology
  • Tsetse Flies / parasitology*

Substances

  • Glycoproteins
  • Lectins, C-Type
  • Polysaccharides
  • Salivary Proteins and Peptides
  • Concanavalin A
  • Glycoside Hydrolases

Grants and funding

This work was supported in part by the GlycoPar Marie Curie Initial Training Network 608295 (to KWK, DS and AA-S; www.ec.europa.eu), and a Ph.D. studentship from the Colombian Department of Science, Technology and Innovation (Colciencias) through the ‘Francisco José de Caldas’ scholarship programme (to KMS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.