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Title: Structural and functional characterisation of salivary glycans from bloodfeeding arthropods
Author: Mondragon Shem, K.
ISNI:       0000 0004 7970 4771
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2019
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The saliva of hematophagous arthropods is a powerful cocktail of substances meant to facilitate bloodfeding, by counteracting the host's healing processes. Insect saliva can also stimulate significant immune responses, but while most research has focused on the proteins it contains, the glycans (sugars) that modify them remain overlooked. As glycans can determine a protein's biological role, they can be responsible for the saliva's effects on pathogens and their transmission. Therefore, in this work I set out to characterize the salivary glycans of ticks (Amblyomma cajennense), mosquitoes (Anopheles gambiae, Aedes aegypti), tsetse flies (Glossina morsitans), sandflies (Lutzomyia longipalpis) and triatomines (Rhodnius prolixus). To do this, I dissected and harvested saliva from each of these arthropods and characterized the sugar structures using a glycomics approaches. This included enzymatic treatment with specific glycosidases, followed by high-performance liquid chromatography analyses in combination with highly sensitive mass spectrometry. It was found that the salivary glycoproteins of these vectors are mostly composed of N-linked mannose-type sugars, with a predominant proportion of paucimannose (short) glycans; the comparison between species shows variations mainly in the abundance of these structures. Interestingly, there were hybrid sugars specific to each organism, with mosquitoes and tick glycoproteins displaying the most striking and potentially immunogenic structures. In particular, I show structural evidence that some of the salivary glycans from A. cajenensis contain terminal a-galactose residues, which may be responsible for the high levels of IgE anti-Gal in patients exposed to several tick bites. Furthermore, overlay assays using either recombinant human mannose receptor or DC-SIGN, on either denatured or native samples, showed that these receptors specifically recognized N-glycans on salivary glycoproteins from all insect species investigated in this thesis, hinting at possible in vivo interactions with macrophages and dendritic cells. It is suggested that the endocytic activity by these cells could have a role in the host clearance (half-life) of the salivary glycoproteins themselves and that these interactions may be responsible for the specific immune responses that modulate transmission of vector-borne pathogens. Finally, the similarities of the glycan structures found in different species suggests the presence of conserved pathways of salivary protein glycosylation.
Supervisor: Acosta Serrano, Alvaro Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral