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Lookup NU author(s): Professor Jeremy LakeyORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Lipopolysaccharide (LPS) O-antigen (O-Ag) is known to limit antibody binding to surface antigens, although the relationship between antibody, O-Ag and other outer-membrane antigens is poorly understood. Here we report, immunization with the trimeric porin OmpD from Salmonella Typhimurium (STmOmpD) protects against infection. Atomistic molecular dynamics simulations indicate this is because OmpD trimers generate footprints within the O-Ag layer sufficiently sized for a single IgG Fab to access. While STmOmpD differs from its orthologue in S. Enteritidis (SEn) by a single amino-acid residue, immunization with STmOmpD confers minimal protection to SEn. This is due to the OmpD-O-Ag interplay restricting IgG binding, with the pairing of OmpD with its native O-Ag being essential for optimal protection after immunization. Thus, both the chemical and physical structure of O-Ag are key for the presentation of specific epitopes within proteinaceous surface-antigens. This enhances combinatorial antigenic diversity in Gram-negative bacteria, while reducing associated fitness costs.
Author(s): Dominguez-Medina CC, Perez-Toledo M, Schager AE, Marshall JL, Cook CN, Bobat S, Hwang H, Chun BJ, Logan E, Bryant JA, Channell WM, Morris FC, Jossi SE, Alshayea A, Rossiter AE, Barrow PA, Horsnell WG, MacLennan CA, Henderson IR, Lakey JH, Gumbart JC, Lopez-Macias C, Bavro VN, Cunningham AF
Publication type: Article
Publication status: Published
Journal: Nature communications
Year: 2020
Volume: 11
Issue: 1
Online publication date: 12/02/2020
Acceptance date: 23/01/2020
Date deposited: 24/02/2020
ISSN (electronic): 2041-1723
Publisher: Nature
URL: https://doi.org/10.1038/s41467-020-14655-9
DOI: 10.1038/s41467-020-14655-9
PubMed id: 32051408
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