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

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

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
12 02 2020
Historique:
received: 05 03 2019
accepted: 23 01 2020
entrez: 14 2 2020
pubmed: 14 2 2020
medline: 24 4 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-14655-9 PMID: 32051408 PMC: PMC7015928
pubmed: 32051408
doi: 10.1038/s41467-020-14655-9
pii: 10.1038/s41467-020-14655-9
pmc: PMC7015928
doi:

Substances chimiques

Antibodies, Bacterial 0
Antigens, Bacterial 0
Bacterial Outer Membrane Proteins 0
Epitopes 0
Immunoglobulin G 0
O Antigens 0
OmpD protein, Salmonella typhimurium 0
Porins 0

Types de publication

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.

Langues

eng

Sous-ensembles de citation

IM

Pagination

851

Subventions

Organisme : Medical Research Council
ID : MR/R005974/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N023706/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P008852/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L009986/1
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM123169
Pays : United States
Organisme : Wellcome Trust
ID : 108372/A/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom

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Auteurs

C Coral Domínguez-Medina (CC)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.
Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.

Marisol Pérez-Toledo (M)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.
Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.
Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI" Mexican Institute for Social Security, Mexico City, Mexico.
ORCID: 0000-0002-5734-255X

Anna E Schager (AE)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.
Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.

Jennifer L Marshall (JL)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.

Charlotte N Cook (CN)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.
Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.

Saeeda Bobat (S)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.
Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.

Hyea Hwang (H)

School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta GA, 30332, USA.

Byeong Jae Chun (BJ)

School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta GA, 30332, USA.
ORCID: 0000-0002-6095-3482

Erin Logan (E)

Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Cape Town, Western Cape, 7925, South Africa.

Jack A Bryant (JA)

Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.

Will M Channell (WM)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.

Faye C Morris (FC)

Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.

Sian E Jossi (SE)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.

Areej Alshayea (A)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.

Amanda E Rossiter (AE)

Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.

Paul A Barrow (PA)

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire, LE12 5RD, UK.

William G Horsnell (WG)

Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Cape Town, Western Cape, 7925, South Africa.

Calman A MacLennan (CA)

Jenner Institute, Nuffield Department of Medicine, Old Road Campus Research Building, Roosevelt Drive, University of Oxford, Oxford, OX3 7DQ, UK.

Ian R Henderson (IR)

Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK.

Jeremy H Lakey (JH)

Institute for Cell and Molecular Biosciences, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK.

James C Gumbart (JC)

School of Physics, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

Constantino López-Macías (C)

Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI" Mexican Institute for Social Security, Mexico City, Mexico.
ORCID: 0000-0003-0530-492X

Vassiliy N Bavro (VN)

School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK. v.bavro@essex.ac.uk.
ORCID: 0000-0003-2330-8924

Adam F Cunningham (AF)

Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK. a.f.cunningham@bham.ac.uk.
Institute of Microbiology and Infection, University of Birmingham, Birmingham, B15 2TT, UK. a.f.cunningham@bham.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antibactériens › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité acquise › Immunité active › Production d'anticorps › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Phénomènes du système immunitaire › Spécificité des anticorps › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes bactériens › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de la membrane externe bactérienne › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Protection croisée › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention primaire › Immunisation › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline G › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Toxines bactériennes › Endotoxines › Lipopolysaccharides › Antigènes O › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux ioniques › Porines › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Maladies de l'animal › Salmonelloses animales › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Bactéries › Proteobacteria › Gammaproteobacteria › Enterobacteriaceae › Salmonella › Salmonella enterica › Salmonella typhimurium › Outer membrane protein size and LPS O-antigen...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence de protéine › Outer membrane protein size and LPS O-antigen...