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  • Shigella flexneri Targets Human Colonic Goblet Cells by O Antigen Binding to Sialyl-Tn and Tn Antigens via Glycan-Glycan Interactions

    Author(s)
    Tran, ENH
    Day, CJ
    McCartney, E
    Poole, J
    Tse, E
    Jennings, MP
    Morona, R
    Griffith University Author(s)
    Jennings, Michael P.
    Day, Christopher J.
    Poole, Jessica
    Year published
    2020
    Metadata
    Show full item record
    Abstract
    Shigella 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 ...
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    Shigella 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.
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    Journal Title
    ACS Infectious Diseases
    Volume
    6
    Issue
    10
    DOI
    https://doi.org/10.1021/acsinfecdis.0c00178
    Subject
    Medical microbiology
    Shigella flexneri
    Tn glycan
    colonic crypts
    glycan−glycan
    goblet cells
    Publication URI
    http://hdl.handle.net/10072/400809
    Collection
    • Journal articles

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