Carbapenem-resistant Klebsiella Pneumoniae Exhibit Variability in Capsular Polysaccharide and Capsule Associated Virulence Traits

J Infect Dis. 2014 Sep 1;210(5):803-13. doi: 10.1093/infdis/jiu157. Epub 2014 Mar 14.

Abstract

Background: Novel therapies are urgently needed to treat carbapenem-resistant Klebsiella pneumoniae (CR-Kp)-mediated infection, which constitute a major health threat in the United States. In order to assess if it is feasible to develop anticapsular antibodies as a potential novel therapy, it is crucial to first systematically characterize capsular polysaccharide (CPS) and virulence traits in these strains.

Methods: Forty CR-Kp were genotyped by pulsed field gel electrophoresis, multilocus sequence typing (MLST), and molecular capsule typing (C-patterns and wzi sequencing). Their biofilm formation, serum resistance, macrophage-mediated killing, and virulence in Galleria mellonella were compared. MAb (1C9) was generated by co-immunization with 2 CPSs, and cross-reactivity was investigated.

Results: MLST assigned 80% of CR-Kp isolates to the ST258-clone. Molecular capsule typing identified new C-patterns, including C200/wzi-154, which was widely represented and associated with blaKPC-3-bearing strains. Heterogeneity was detected in biofilm formation and macrophage-mediated killing. Differences in serum resistance correlated with virulence in G. mellonella. ST258 strains carrying blaKPC-3 were less virulent than those with blaKPC-2. MAb 1C9 cross-reacted with 58% of CR-Kp CPSs.

Conclusions: CR-Kp ST258 strains exhibit variability of virulence-associated traits. Differences were associated with the type of KPC gene and CPS. Identification of cross-reacting anti-CPS mAbs encourages their development as adjunctive therapy.

Keywords: Klebsiella pneumoniae; adjuvant therapy; carbapenem resistance; virulence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antibodies, Bacterial / immunology
  • Bacterial Capsules / metabolism*
  • Biofilms / growth & development
  • Blood Bactericidal Activity
  • Carbapenems / pharmacology*
  • Female
  • Genotype
  • Humans
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / classification
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / isolation & purification
  • Klebsiella pneumoniae / pathogenicity*
  • Lepidoptera
  • Macrophages / immunology
  • Male
  • Mice, Inbred BALB C
  • Middle Aged
  • Molecular Typing
  • Retrospective Studies
  • Survival Analysis
  • United States
  • Virulence
  • beta-Lactam Resistance*

Substances

  • Anti-Bacterial Agents
  • Antibodies, Bacterial
  • Carbapenems