title: The diversity ofKlebsiella pneumoniaesurface polysaccharides.
abstract: Klebsiella pneumoniaeis considered an urgent health concern due to the emergence of multi-drug-resistant strains for which vaccination offers a potential remedy. Vaccines based on surface polysaccharides are highly promising but need to address the high diversity of surface-exposed polysaccharides, synthesized as O-antigens (lipopolysaccharide, LPS) and K-antigens (capsule polysaccharide, CPS), present inK. pneumoniae. We present a comprehensive and clinically relevant study of the diversity of O- and K-antigen biosynthesis gene clusters across a global collection of over 500K. pneumoniaewhole-genome sequences and the seroepidemiology of human isolates from different infection types. Our study defines the genetic diversity of O- and K-antigen biosynthesis cluster sequences across this collection, identifying sequences for known serotypes as well as identifying novel LPS and CPS gene clusters found in circulating contemporary isolates. Serotypes O1, O2 and O3 were most prevalent in our sample set, accounting for approximately 80 % of all infections. In contrast, K serotypes showed an order of magnitude higher diversity and differ among infection types. In addition we investigated a potential association of O or K serotypes with phylogenetic lineage, infection type and the presence of known virulence genes. K1 and K2 serotypes, which are associated with hypervirulentK. pneumoniae, were associated with a higher abundance of virulence genes and more diverse O serotypes compared to other common K serotypes.
authors.affiliation: 1​LimmaTech Biologics AG, Schlieren, Switzerland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Follador
authors.affiliation: 2​The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Eva
authors.initials: E
authors.lastname: Heinz
authors.affiliation: 3​Centre for Systems Genomics, University of Melbourne, Parkville, Victoria, Australia.|4​Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Wyres
authors.affiliation: 5​National Infection Service Public Health England, London, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellington
authors.affiliation: 1​LimmaTech Biologics AG, Schlieren, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Kowarik
authors.affiliation: 3​Centre for Systems Genomics, University of Melbourne, Parkville, Victoria, Australia.|4​Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.affiliation: 2​The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.|6​London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007711:Klebsiella pneumoniae / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D019081:O Antigens / Q000235:genetics; D010802:Phylogeny; D016036:Seroepidemiologic Studies; D065288:Serogroup; D014774:Virulence / Q000235:genetics*
chemical_list: D000942:Antigens, Bacterial; D000954:Antigens, Surface; C030659:K antigens; D019081:O Antigens
keywords: K antigen and O antigen; Klebsiella pneumoniae; seroepidemiology; surface polysaccharide; vaccine target