Alpha-Gal and Cross-Reactive Carbohydrate Determinants in the N-Glycans of Salivary Glands in the Lone Star Tick, Amblyomma americanum.

Yoonseong Park,Donghun Kim,Ladislav Šimo,Stephanie Archer-Hartmann,Kristof De Schutter,Gunavanthi Boorgula,Parastoo Azadi,Guy Smagghe

doi:10.3390/vaccines8010018

Abstract

Ticks are important ectoparasites and vectors of numerous human and animal pathogens. Ticks secrete saliva that contains various bioactive materials to evade the host defense system, and often facilitates the pathogen transmission. In addition, the Lone star tick saliva is thought to be the sensitizer in red meat allergy that is characterized by an allergic reaction to glycan moieties carrying terminal galactose-alpha-1,3-galactose (aGal). To assess N-glycome of Amblyomma americanum, we examined the N-glycan structures in male and female salivary glands at three different feeding stages and in carcasses of partially fed lone star ticks. We also surveyed the genes involved in the N-glycosylation in the tick species. The aGal epitopes and cross-reactive carbohydrate determinants (CCD) increases over time after the onset of blood feeding in both male and female A. americanum. These CCDs include xylosylation of the core mannose, 1,3-mono and 1,3- and 1,6-difucosylations of the basal GlcNac and mono- or diantennary aGal. Combinations of both xylosylation and aGal and fucosylation and aGal were also found on the N-glycan structures. While the enzymes required for the early steps of the N-glycosylation pathway are quite conserved, the enzymes involved in the later stages of N-glycan maturation in the Golgi apparatus are highly diverged from those of insects. Most of all, we propose that the aGal serves as a molecular mimicry of bioactive proteins during tick feedings on mammalian hosts, while it contributes as a sensitizer of allergy in atypical host human.

Highlights

Protein glycosylation, or the attachment ofsaccharides to the amino acid residues Asn (N-glycosylation) and Ser or Thr (O-glycosylation), is the most common and important post-translational modification
Based on the results showing high levels of aGal in the salivary glands (SGs) during blood feeding, we propose that ticks use aGal as a molecular mimicry to evade the immune system of nonprimate hosts, while the aGal may function as an allergy sensitizer in the atypical host human
To explore the effect of feeding on the N-glycan profile of the lone star tick, male and female ticks were allowed to feed in an artificial membrane feeding chamber [23,24]

Summary

Introduction

The attachment of (oligo)saccharides to the amino acid residues Asn (N-glycosylation) and Ser or Thr (O-glycosylation), is the most common and important post-translational modification. Protein glycosylation is essential in all eukaryotic cells and is involved in multiple crucial processes in the cell This is reflected in the conservation of glycosylation sites and glycan structures [2,3] and essential roles of the enzymes involved in glycan biosynthesis and maturation [4,5]. Vaccines 2020, 8, 18 of N-glycosylation are well conserved throughout different taxa of eukaryotes, divergence is observed at the subsequent steps generating interspecies and intraspecies specific N-glycan structures [6]. This diversity of glycans in different organisms involves evolutionary selection processes with the selection pressure on the presence/absence of functional metabolic genes, enzyme activities, and their substrate specificities. The general evolutionary pattern of N-glycan likely involved drift in neutral or near-neutral evolution based on the high variations in closely related taxa, whereas the parts of

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