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Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Associated disease: infection due to Klebsiella pneumoniae [ICD11: XN741

]

NCBI PubMed ID: 29760533
Publication DOI: 10.1038/s41590-018-0106-2
Journal NLM ID: 100941354
Publisher: New York, NY: Nature America Publishing
Correspondence: h.wardemann

dkfz.de
Institutions: Max Planck Research Group Molecular Immunology, Max Planck Institute for Infection Biology, Berlin, Germany, Division of B Cell Immunology, German Cancer Research Center, Heidelberg, Germany, Arsanis Biosciences, Vienna, Austria, Department of Immunochemistry, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences, Wroclaw, Poland, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany, Department of General and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany, Department of General, Abdominal and Minimal Invasive Surgery, Hospital Salem, Heidelberg, Germany, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany, Department of General, Visceral, Vascular and Pediatric Surgery, Saarland University Medical Center, Homburg, Germany, Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany, Department of Infectious Diseases, Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany

Humoral immune responses to microbial polysaccharide surface antigens can prevent bacterial infection but are typically strain specific and fail to mediate broad protection against different serotypes. Here we describe a panel of affinity-matured monoclonal human antibodies from peripheral blood immunoglobulin M-positive (IgM(+)) and IgA(+) memory B cells and clonally related intestinal plasmablasts, directed against the lipopolysaccharide (LPS) O-antigen of Klebsiella pneumoniae, an opportunistic pathogen and major cause of antibiotic-resistant nosocomial infections. The antibodies showed distinct patterns of in vivo cross-specificity and protection against different clinically relevant K. pneumoniae serotypes. However, cross-specificity was not limited to K. pneumoniae, as K. pneumoniae-specific antibodies recognized diverse intestinal microbes and neutralized not only K. pneumoniae LPS but also non-K. pneumoniae LPS. Our data suggest that the recognition of minimal glycan epitopes abundantly expressed on microbial surfaces might serve as an efficient humoral immunological mechanism to control invading pathogens and the large diversity of the human microbiota with a limited set of cross-specific antibodies.

Lipopolysaccharide, O-antigen, Serotypes, antibodies, antigens, B cell, immunoglobulin, Klebsiella pneumoniae, immune response, humoral immune response

Structure type: oligomer
Location inside paper: fig.S1a, O3-CP
Trivial name: biotinylated O3 O-antigen
Compound class: core oligosaccharide with O-units
Contained glycoepitopes: IEDB_115576,IEDB_130650,IEDB_130701,IEDB_135813,IEDB_136104,IEDB_137340,IEDB_140116,IEDB_141111,IEDB_141795,IEDB_141807,IEDB_141830,IEDB_143632,IEDB_144983,IEDB_151531,IEDB_152206,IEDB_153756,IEDB_164174,IEDB_164175,IEDB_164176,IEDB_164480,IEDB_174840,IEDB_2189047,IEDB_241100,IEDB_76933,IEDB_983930,SB_136,SB_196,SB_197,SB_44,SB_67,SB_72

Methods: ELISA, serological methods, genetic methods, immunoblotting, serotyping, flow cytometry analysis
Biological activity: serological data
Comments, role: structure from ref. [5] Vinogradov et al., 2002 [DOI:10.1074/jbc.M202683200]; chemical repeat frame is different in the paper (fig.1 and fig.S1); biotin = 5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoic acid

Related record ID(s): 12766, 12767, 12768, 12769, 12770, 12968
NCBI Taxonomy refs (TaxIDs): 573
Show glycosyltransferases

There is only one chemically distinct structure:

COP(=O)(O)O[C@@H]1[C@H](O)[C@@H](O[C@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2O[C@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2O[C@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2O[C@@H]2[C@H](O)[C@@H](O[C@@H]3[C@H](O)[C@@H](O[C@H]4[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]4O[C@H]4[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]4O[C@H]4[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]4O[C@@H]4[C@H](O)[C@@H](O[C@@H]5[C@H](O)[C@@H](O[C@H]6[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]6O[C@H]6[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]6O[C@H]6[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]6O[C@@H]6[C@H](O)[C@@H](O[C@@H]7[C@H](O)[C@@H](O[C@H]8[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]8O[C@H]8[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]8O[C@H]8[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]8O[C@@H]8[C@H](O)[C@@H](O[C@@H]9[C@H](O)[C@@H](O[C@@H]%10[C@H](O)[C@@H](O[C@@H]%11[C@H](O)[C@@H](O[C@H]%12[C@H](O)[C@@H](CO)O[C@@H](O[C@@H]%13[C@H](O[C@H]%14O[C@H]([C@@H](O)CO)[C@@H](O)[C@H](O)[C@@H]%14O)C[C@](OCCOCCOCCOCCOC(=O)CCCC[C@@H]%14SC[C@@H]%15NC(=O)N[C@H]%14%15)(C(=O)O)O[C@@H]%13[C@H](O)CO)[C@@H]%12NC(C)=O)O[C@H](CO)[C@H]%11O)O[C@H](CO)[C@H]%10O)O[C@H](CO)[C@H]9O)O[C@H](CO)[C@H]8O)O[C@H](CO)[C@H]7O)O[C@H](CO)[C@H]6O)O[C@H](CO)[C@H]5O)O[C@H](CO)[C@H]4O)O[C@H](CO)[C@H]3O)O[C@H](CO)[C@H]2O)O[C@H](CO)[C@H]1O

SVG MW SMILES 3D mol Ionize

Warning = sub-repeat ending at xXEtg: unknown unit count was assumed to be 3
Warning = sub-repeat ending at aDManp: unknown unit count was assumed to be 3