Abstract
Fucosylated glycans of the parasitic flatworm Schistosoma mansoni play key roles in its development and immunobiology. In the present study we used a genome-wide homology-based bioinformatics approach to search for genes that contribute to fucosylated glycan expression in S. mansoni, specifically the α2-, α3-, and α6-fucosyltransferases (FucTs), which transfer L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. We identified and in silico characterized several novel schistosome FucT homologs, including six α3-FucTs and six α6-FucTs, as well as two protein O-FucTs that catalyze the unrelated transfer of L-fucose to serine and threonine residues of epidermal growth factor- and thrombospondin-type repeats. No α2-FucTs were observed. Primary sequence analyses identified key conserved FucT motifs as well as characteristic transmembrane domains, consistent with their putative roles as fucosyltransferases. Most genes exhibit alternative splicing, with multiple transcript variants generated. A phylogenetic analysis demonstrated that schistosome α3- and α6-FucTs form monophyletic clades within their respective gene families, suggesting multiple gene duplications following the separation of the schistosome lineage from the main evolutionary tree. Quantitative decreases in steady-state transcript levels of some FucTs during early larval development suggest a possible mechanism for differential expression of fucosylated glycans in schistosomes. This study systematically identifies the complete repertoire of FucT homologs in S. mansoni and provides fundamental information regarding their genomic organization, genetic variation, developmental expression, and evolutionary history.
Highlights
Chronic schistosomiasis in mammalian hosts, including humans, results from granulomatous inflammation in response to parasite eggs that accumulate in host tissues [1]
An exhaustive homology search of the Schistosoma mansoni database (SchistoDB; [35]) in conjunction with comprehensive sequence analyses generated a non-redundant list of 15 genes with predicted roles in a3, a6- and protein O-fucosylation
Homology-based searches failed to detect any sequences in the SchistoDB corresponding to FucT-VII, the only other FucT homolog reported from S. mansoni [19]
Summary
Chronic schistosomiasis in mammalian hosts, including humans, results from granulomatous inflammation in response to parasite eggs that accumulate in host tissues [1]. Previous studies in Schistosoma mansoni suggest that surface-expressed and secreted/ excreted carbohydrates are key elements that drive this pathogenesis, with oligosaccharides playing roles in egg sequestration, Th2 immune biasing, granuloma formation and modulation, and strong antibody responses in human hosts [2,3]. A3- and a6-linked fucoses occur alone or in combination as substituents of the chitobiose core (-GlcNAcb1-4GlcNAcb1-) in paucimannosidic and complex type N-glycans [11]. Such core modifications, especially a3fucosylation, induce strong allergic responses in mammalian hosts and account for the interspecific immunological cross-reactivity observed among plant, insect, and helminth glycoproteins [12,13]. To better understand the developmental expression of immunologically important fucosylated glycans in S. mansoni, basic information is needed regarding the repertoire of Golgi-localized fucosyltransferases (FucTs), the a2-, a3- and a6-FucTs, which transfer L-fucose from a guanosine diphosphate (GDP)-L-fucose donor to an oligosaccharide acceptor, creating a2, a3, or a6 linkages
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