Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface

C. Coral Domínguez-Medina, Marisol Pérez-Toledo, Anna E. Schager, Jennifer L. Marshall, Charlotte N. Cook, Saeeda Bobat, Hyea Hwang, Byeong Jae Chun, Erin Logan, Jack A. Bryant, Will M. Channell, Faye C. Morris, Sian E. Jossi, Areej Alshayea, Amanda E. Rossiter, Paul A. Barrow, William G. Horsnell, Calman A. MacLennan, Ian R. Henderson, Jeremy H. Lakey, James C. Gumbart, Constantino López-Macías, Vassiliy N. Bavro () and Adam F. Cunningham ()
Additional contact information
C. Coral Domínguez-Medina: University of Birmingham
Marisol Pérez-Toledo: University of Birmingham
Anna E. Schager: University of Birmingham
Jennifer L. Marshall: University of Birmingham
Charlotte N. Cook: University of Birmingham
Saeeda Bobat: University of Birmingham
Hyea Hwang: Georgia Institute of Technology
Byeong Jae Chun: Georgia Institute of Technology
Erin Logan: University of Cape Town
Jack A. Bryant: University of Birmingham
Will M. Channell: University of Birmingham
Faye C. Morris: University of Birmingham
Sian E. Jossi: University of Birmingham
Areej Alshayea: University of Birmingham
Amanda E. Rossiter: University of Birmingham
Paul A. Barrow: University of Nottingham
William G. Horsnell: University of Cape Town
Calman A. MacLennan: University of Oxford
Ian R. Henderson: University of Birmingham
Jeremy H. Lakey: University of Newcastle
James C. Gumbart: Georgia Institute of Technology
Constantino López-Macías: Specialties Hospital, National Medical Centre “Siglo XXI” Mexican Institute for Social Security
Vassiliy N. Bavro: University of Essex, Wivenhoe Park
Adam F. Cunningham: University of Birmingham

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14655-9

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