Domínguez-Medina, C Coral and Pérez-Toledo, Marisol and Schager, Anna E and Marshall, Jennifer L and Cook, Charlotte N and Bobat, Saeeda and Hwang, Hyea and Chun, Byeong Jae and Logan, Erin and Bryant, Jack A and Channell, Will M and Morris, Faye C and Jossi, Sian E and Alshayea, Areej and Rossiter, Amanda E and Barrow, Paul A and Horsnell, William G and MacLennan, Calman A and Henderson, Ian R and Lakey, Jeremy H and Gumbart, James C and López-Macías, Constantino and Bavro, Vassiliy N and Cunningham, Adam F (2020) Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface. Nature Communications, 11 (1). 851-. DOI https://doi.org/10.1038/s41467-020-14655-9
Domínguez-Medina, C Coral and Pérez-Toledo, Marisol and Schager, Anna E and Marshall, Jennifer L and Cook, Charlotte N and Bobat, Saeeda and Hwang, Hyea and Chun, Byeong Jae and Logan, Erin and Bryant, Jack A and Channell, Will M and Morris, Faye C and Jossi, Sian E and Alshayea, Areej and Rossiter, Amanda E and Barrow, Paul A and Horsnell, William G and MacLennan, Calman A and Henderson, Ian R and Lakey, Jeremy H and Gumbart, James C and López-Macías, Constantino and Bavro, Vassiliy N and Cunningham, Adam F (2020) Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface. Nature Communications, 11 (1). 851-. DOI https://doi.org/10.1038/s41467-020-14655-9
Domínguez-Medina, C Coral and Pérez-Toledo, Marisol and Schager, Anna E and Marshall, Jennifer L and Cook, Charlotte N and Bobat, Saeeda and Hwang, Hyea and Chun, Byeong Jae and Logan, Erin and Bryant, Jack A and Channell, Will M and Morris, Faye C and Jossi, Sian E and Alshayea, Areej and Rossiter, Amanda E and Barrow, Paul A and Horsnell, William G and MacLennan, Calman A and Henderson, Ian R and Lakey, Jeremy H and Gumbart, James C and López-Macías, Constantino and Bavro, Vassiliy N and Cunningham, Adam F (2020) Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface. Nature Communications, 11 (1). 851-. DOI https://doi.org/10.1038/s41467-020-14655-9
Abstract
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.
Item Type: | Article |
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Uncontrolled Keywords: | Animals; Mice; Salmonella typhimurium; Salmonella Infections, Animal; Disease Models, Animal; O Antigens; Bacterial Outer Membrane Proteins; Porins; Immunoglobulin G; Antibodies, Bacterial; Antigens, Bacterial; Epitopes; Immunization; Sequence Analysis, Protein; Antibody Formation; Antibody Specificity; Protein Conformation; Models, Molecular; Cross Protection |
Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 29 Apr 2020 08:44 |
Last Modified: | 07 Aug 2024 20:44 |
URI: | http://repository.essex.ac.uk/id/eprint/27384 |
Available files
Filename: Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface.pdf
Licence: Creative Commons: Attribution 3.0