title: D-galactan II is an immunodominant antigen in O1 lipopolysaccharide and affects virulence in Klebsiella pneumoniae: implication in vaccine design.
abstract: In the O1 strain of Klebsiella, the lipopolysaccharide (LPS) O-antigen is composed of D-galactan I and D-galactan II. Although the composition of the O1 antigen of Klebsiella was resolved more than two decades, the genetic locus involved in the biosynthesis of D-galactan II and the role of D-galactan II in bacterial pathogenesis remain unclear. Here, we report the identification of the D-galactan II-synthesizing genes by screening a transposon mutant library of an acapsulated Klebsiella pneumoniae O1 strain with bacteriophage. K. pneumoniae strain deleted for wbbY exhibited abrogated D-galactan II production; altered serum resistance and attenuation of virulence. Serologic analysis of K. pneumoniae clinical isolates demonstrated that D-galactan II was more prevalent in community-acquired pyogenic liver abscess (PLA)-causing strains than in non-tissue-invasive strains. WbbY homologs, WbbZ homologs, and lipopolysaccharide structures based on D-galactan II also were present in several Gram-negative bacteria. Immunization of mice with the magA-mutant (K(-) 1 O1) (that is, with a LPS D-galactan II-producing strain) provided protection against infection with an O1:K2 PLA strain. Our findings indicate that both WbbY and WbbZ homologs are sufficient for the synthesis of D-galactan II. D-galactan II represents an immunodominant antigen; is conserved among multiple species of Gram-negative bacteria and could be a useful vaccine candidate.
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine Taipei, Taiwan.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Hsieh
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Taipei, Taiwan.
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Wu
authors.affiliation: The Institute of Biological Chemistry, Academia Sinica Taipei, Taiwan.
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Yang
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine Taipei, Taiwan.
authors.forename: Chun-Tang
authors.initials: CT
authors.lastname: Chen
authors.affiliation: The Institute of Biological Chemistry, Academia Sinica Taipei, Taiwan.
authors.forename: Tzu-Chi
authors.initials: TC
authors.lastname: Lou
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine Taipei, Taiwan.
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Chen
authors.affiliation: The Institute of Biological Chemistry, Academia Sinica Taipei, Taiwan.
authors.forename: Shih-Hsiung
authors.initials: SH
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Taipei, Taiwan.
authors.forename: Jin-Chuan
authors.initials: JC
authors.lastname: Sheu
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine Taipei, Taiwan ; Department of Internal Medicine, National Taiwan University Hospital Taipei, Taiwan.
authors.forename: Jin-Town
authors.initials: JT
authors.lastname: Wang
keywords: D-galactan II; Klebsiella pneumoniae; immunodominant antigen; lipopolysaccharide; vaccine