title: Lipopolysaccharide O-antigen promotes persistent murine bacteremia.
abstract: Bacteremia is a common complication of pneumonia with Klebsiella pneumoniae. In the previous work, we have shown that the lipopolysaccharide (LPS) O-antigen in K. pneumoniae O1:K2 contributes to lethality during pneumonia in part by promoting bacteremia. In the current work, we studied an O-antigen-deficient K. pneumoniae strain to further evaluate this polysaccharide's role in bloodstream infection. Cultured macrophage and murine bacteremia models were studied. In vitro, O-antigen-deficient bacteria, compared with wild-type organisms, were stronger activators of the murine alveolar macrophage cell line MH-S as assessed by nuclear localization of RelA/p65 and by secretion of cytokines and chemokines. O-antigen-deficient Klebsiellae were also more susceptible to killing by murine neutrophils. In vivo, the absence of O-antigen allowed more rapid and complete clearance of bacteria from the bloodstream, liver, and spleen after intravenous injection in mice. Survival was also greater among animals infected with bacteria missing the O-antigen. Gene expression profiling (via reverse transcriptase-polymerase chain reaction of 84 inflammatory mediator complementary DNA) revealed that by 24 h postinfection, the livers and spleens of animals infected with O-antigen-deficient organisms had significantly downregulated cytokine and chemokine expression compared with wild-type infected animals. The O-antigen surface carbohydrate of O1:K2 serotype K. pneumoniae appears to contribute to bacterial virulence by lessening the activation of macrophages, conveying resistance to killing by neutrophils, and by promoting persistent infection in the blood, liver, and spleen after the onset of bacteremia.
authors.affiliation: Department of Emergency Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Joanelle Z
authors.initials: JZ
authors.lastname: Lugo
authors.forename: Sarah
authors.initials: S
authors.lastname: Price
authors.forename: Julia E
authors.initials: JE
authors.lastname: Miller
authors.forename: Itzhak
authors.initials: I
authors.lastname: Ben-David
authors.forename: Vija  A
authors.initials: V
authors.lastname: Merrill
authors.forename: Vija J
authors.initials: VJ
authors.lastname: Merrill
authors.forename: Peter
authors.initials: P
authors.lastname: Mancuso
authors.forename: Jason B
authors.initials: JB
authors.lastname: Weinberg
authors.forename: John G
authors.initials: JG
authors.lastname: Younger
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000276:immunology*; D002460:Cell Line; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007710:Klebsiella Infections / Q000235:genetics / Q000276:immunology*; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D019081:O Antigens / Q000235:genetics / Q000276:immunology / Q000633:toxicity*; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology*; D013997:Time Factors
chemical_list: D019081:O Antigens