Data Sheet 1_Chemical inhibition of α-mannosidase in S. mansoni schistosomula leads to reshaped N-glycosylation associated with developmental alterations.pdf

We first analysed the effect of the inhibitors on schistosomula motility and phenotype, and showed that there was no overt toxicity linked to these compounds. Next, we examined the schistosomula N-glycosylation profiles during six weeks of culture. Within the first week (W1), the N-glycosylation changed dynamically in the schistosomula and exposure to inhibitors led to distinct profiles compared to the control.

Control parasites were marked by oligomannose (30%) and complex (60%) N-glycans, kifunensine treatment led to a high proportion of oligomannose N-glycans (72%), specifically M8 and M9, and swainsonine-treated schistosomula were characterised by oligomannose (44%), hybrid (11%) N-glycans and free N-glycans with one core-GlcNAc (16%) at W1 post-compound treatment. Continued treatment conserved the distinct profiles, while discontinuation of treatment after W1 caused the N-glycans of kifunensine and swainsonine schistosomula to return to a profile similar to controls at W3.

Interestingly, schistosomula treated continuously with kifunensine developed local oedema from W4 onwards, which was most profound at W6. However, discontinued treatment after W1 did not lead to a visible phenotype at W4 or later. In conclusion, prolonged alterations in schistosomula N-glycosylation led to disturbed development whereas short term glycan changes during the first week only, did not affect the parasite’s normal development.

Our data indicate that glyco-remodelled live schistosomes provide an attractive approach to study the contribution of glycans in intra-mammalian parasite development and survival.</p>