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


C. Coral


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


Vassiliy N. Bavro

Adam F. Cunningham


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.


Domínguez-Medina, C. C., Pérez-Toledo, M., Schager, A. E., Marshall, J. L., Cook, C. N., Bobat, S., …Cunningham, A. F. (2020). Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface. Nature Communications, 11, Article 851.

Journal Article Type Article
Acceptance Date Jan 23, 2020
Online Publication Date Feb 12, 2020
Publication Date 2020-12
Deposit Date Nov 9, 2020
Publicly Available Date Nov 12, 2020
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 11
Article Number 851
Keywords General Biochemistry, Genetics and Molecular Biology; General Physics and Astronomy; General Chemistry
Public URL
Publisher URL
Additional Information Received: 5 March 2019; Accepted: 23 January 2020; First Online: 12 February 2020; : In 2008, Prof. Cunningham patented OmpD as a component of a vaccine against nontyphoidal Salmonella infections. The remaining authors declare no competing interests.


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