title: Lipopolysaccharide O1 antigen contributes to the virulence in Klebsiella pneumoniae causing pyogenic liver abscess.
abstract: Klebsiella pneumoniae is the common cause of a global emerging infectious disease, community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) and lipopolysaccharide (LPS) are critical for this microorganism's ability to spread through the blood and to cause sepsis. While CPS type K1 is an important virulence factor in K. pneumoniae causing PLA, the role of LPS in PLA is not clear. Here, we characterize the role of LPS O antigen in the pathogenesis of K. pneumoniae causing PLA. NTUH-K2044 is a LPS O1 clinical strain; the presence of the O antigen was shown via the presence of 1,3-galactan in the LPS, and of sequences that align with the wb gene cluster, known to produce O-antigen. Serologic analysis of K. pneumoniae clinical isolates demonstrated that the O1 serotype was more prevalent in PLA strains than that in non-tissue-invasive strains (38/42 vs. 9/32, P<0.0001). O1 serotype isolates had a higher frequency of serum resistance, and mutation of the O1 antigen changed serum resistance in K. pneumoniae. A PLA-causing strain of CPS capsular type K2 and LPS serotype O1 (i.e., O1:K2 PLA strain) deleted for the O1 synthesizing genes was profoundly attenuated in virulence, as demonstrated in separate mouse models of septicemia and liver abscess. Immunization of mice with the K2044 magA-mutant (K(1) (-) O(1)) against LPS O1 provided protection against infection with an O1:K2 PLA strain, but not against infection with an O1:K1 PLA strain. Our findings indicate that the O1 antigen of PLA-associated K. pneumoniae contributes to virulence by conveying resistance to serum killing, promoting bacterial dissemination to and colonization of internal organs after the onset of bacteremia, and could be a useful vaccine candidate against infection by an O1:K2 PLA strain.
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Hsieh
authors.forename: Tzu-Lung
authors.initials: TL
authors.lastname: Lin
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Yang
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Wu
authors.forename: Yi-Jiun
authors.initials: YJ
authors.lastname: Pan
authors.forename: Shih-Hsiung
authors.initials: SH
authors.lastname: Wu
authors.forename: Jin-Town
authors.initials: JT
authors.lastname: Wang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D016667:Bacterial Capsules / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005838:Genotype; D007106:Immune Sera / Q000276:immunology; D015151:Immunoblotting; D053208:Kaplan-Meier Estimate; D007710:Klebsiella Infections / Q000276:immunology* / Q000517:prevention & control; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000472:pathogenicity*; D008070:Lipopolysaccharides / Q000378:metabolism*; D046290:Liver Abscess, Pyogenic / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011135:Polysaccharides, Bacterial; D017422:Sequence Analysis, DNA; D012703:Serotyping; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D017931:DNA Primers; D007106:Immune Sera; D008070:Lipopolysaccharides; C501254:MagA protein, Klebsiella pneumoniae; D011135:Polysaccharides, Bacterial; D037521:Virulence Factors; C036962:capsular polysaccharide K1