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

Carbapenem-resistant Klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits.

Author information

1
Department of Medicine Infectious Disease Division Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York.
2
Public Health Research Institute Tuberculosis Center, NJMS-Rutgers University, Newark, New Jersey.
3
Institut Pasteur, Microbial Evolutionary Genomics CNRS, UMR3525, Paris, France;
4
Department of Clinical Microbiology Montefiore Medical Center, Bronx, New York.

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

PMID:
24634498
PMCID:
PMC4432395
DOI:
10.1093/infdis/jiu157
[Indexed for MEDLINE]
Free PMC Article

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