Shigella flexneri targets human colonic goblet cells by O antigen binding to Sialyl-Tn and Tn antigens via glycan-glycan interactions

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dc.contributor.authorTran, E.N.H.
dc.contributor.authorDay, C.J.
dc.contributor.authorMcCartney, E.
dc.contributor.authorPoole, J.
dc.contributor.authorTse, E.
dc.contributor.authorJennings, M.P.
dc.contributor.authorMorona, R.
dc.date.issued2020
dc.description.abstractShigella flexneri targets colonic cells in humans to initiate invasive infection processes that lead to dysentery, and direct interactions between their lipopolysaccharide O antigens and blood group A related glycans are involved in the cell adherence interactions. Here, we show that treatment with Tn and sialyl-Tn glycans, monoclonal antibodies and lectins reactive to Tn/sialyl-Tn, and luteolin (a Tn antigen synthesis inhibitor) all significantly inhibited S. flexneri adherence and invasion of cells in vitro. Surface plasmon resonance analysis showed that lipopolysaccharide O antigen had a high affinity interaction with Tn/sialyl-Tn. Immunofluorescence probing of human colon tissue with antibodies detected expression of Tn/sialyl-Tn by MUC2 producing goblet cells (GCs), and S. flexneri incubated with human colon tissue colocalized with GCs. Our findings demonstrate that S. flexneri targets GCs in the human colonic crypts via glycan-glycan interactions, establishing new insight into the infection process in humans.
dc.description.statementofresponsibilityElizabeth Ngoc Hoa Tran, Christopher J. Day, Erin McCartney, Jessica Poole, Edmund Tse, Michael P. Jennings, and Renato Morona
dc.identifier.citationACS Infectious Diseases, 2020; 6(10):2604-2615
dc.identifier.doi10.1021/acsinfecdis.0c00178
dc.identifier.issn2373-8227
dc.identifier.issn2373-8227
dc.identifier.orcidTran, E.N.H. [0000-0003-1644-2287]
dc.identifier.orcidMorona, R. [0000-0001-7009-7440]
dc.identifier.urihttp://hdl.handle.net/2440/129457
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1108124
dc.rights© 2020 American Chemical Society
dc.source.urihttps://doi.org/10.1021/acsinfecdis.0c00178
dc.subjectShigella flexneri; Tn glycan; sialyl-Tn glycan; colonic crypts; goblet cells; glycan−glycan
dc.titleShigella flexneri targets human colonic goblet cells by O antigen binding to Sialyl-Tn and Tn antigens via glycan-glycan interactions
dc.typeJournal article
pubs.publication-statusPublished

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