title: Klebsiella pneumoniae peptidoglycan-associated lipoprotein and murein lipoprotein contribute to serum resistance, antiphagocytosis, and proinflammatory cytokine stimulation.
abstract: BACKGROUND
  Peptidoglycan-associated lipoprotein (Pal), murein lipoprotein (LppA), and outer membrane protein A (OmpA) are dominant outer membrane proteins (OMPs) that are released by gram-negative bacteria during sepsis. OMPs are implicated in the maintenance of cell envelope integrity. Here, we characterize the roles of these OMPs in pathogenesis during bacteremia caused by Klebsiella pneumoniae.
  
  
  METHODS
  pal-, lppA-, and ompA-deficient K. pneumoniae strains were constructed using an unmarked deletion method. Serum sensitivity, antiphagocytosis activity, outer membrane permeability, and sensitivity to anionic detergents and antimicrobial polypeptides were determined for these OMP gene deletion mutants. The ability of these OMP gene deletion mutants to induce immune responses was compared with that of the wild-type strain in a bacteremic mouse model.
  
  
  RESULTS
  Klebsiella pneumoniae strains deleted for pal or lppA exhibited reduced protection from serum killing and phagocytosis; perturbation to the outer membrane permeability barrier and hypersensitivity to bile salts and sodium dodecyl sulfate. The strain mutated for lppA had reduced ability to activate Toll-like receptor 4. Immunization of mice with the pal or lppA mutant provided protection against infection by the wild-type strain.
  
  
  CONCLUSIONS
  Our findings indicate that K. pneumoniae Pal and LppA proteins are important in the maintenance of cell integrity, contribute to virulence, and could be used as attenuated vaccines.
authors.affiliation: Department of Microbiology, National Taiwan University College of Medicine.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Hsieh
authors.forename: Ju-Yun
authors.initials: JY
authors.lastname: Liu
authors.forename: Yi-Jiun
authors.initials: YJ
authors.lastname: Pan
authors.forename: Meng-Chuan
authors.initials: MC
authors.lastname: Wu
authors.forename: Tzu-Lung
authors.initials: TL
authors.lastname: Lin
authors.forename: Yen-Te
authors.initials: YT
authors.lastname: Huang
authors.forename: Jin-Town
authors.initials: JT
authors.lastname: Wang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002463:Cell Membrane Permeability; D016207:Cytokines / Q000276:immunology*; D003902:Detergents / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D007710:Klebsiella Infections / Q000276:immunology / Q000517:prevention & control; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D010457:Peptidoglycan / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D010641:Phenotype; D014774:Virulence / Q000235:genetics / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D003902:Detergents; D018836:Inflammation Mediators; D010457:Peptidoglycan
keywords: Klebsiella pneumoniae; murein lipoprotein; outer membrane protein A; outer membrane proteins; peptidoglycan-associated lipoprotein