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

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.

• Authors: 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, Adam F Cunningham
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 851 (02 12 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 32051408 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Bacterial
• Antigens, Bacterial
• Bacterial Outer Membrane Proteins
• Epitopes
• Immunoglobulin G
• O Antigens
• OmpD protein, Salmonella typhimurium
• Porins

Topics

• Animals
• Antibodies, Bacterial (blood, immunology)
• Antibody Formation
• Antibody Specificity
• Antigens, Bacterial (immunology)
• Bacterial Outer Membrane Proteins (chemistry, genetics, immunology)
• Cross Protection
• Disease Models, Animal
• Epitopes (chemistry, immunology)
• Immunization
• Immunoglobulin G (blood)
• Mice
• Models, Molecular
• O Antigens (chemistry, genetics, immunology)
• Porins (chemistry, genetics, immunology)
• Protein Conformation
• Salmonella Infections, Animal (immunology, prevention & control)
• Salmonella typhimurium (immunology)
• Sequence Analysis, Protein