Dataset Information

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

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.

SUBMITTER: Diago-Navarro E

PROVIDER: S-EPMC4432395 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Diago-Navarro Elizabeth E Chen Liang L Passet Virginie V Burack Seth S Ulacia-Hernando Amaia A Kodiyanplakkal Rosy Priya RP Levi Michael H MH Brisse Sylvain S Kreiswirth Barry N BN Fries Bettina C BC

The Journal of infectious diseases 20140314 5

<h4>Background</h4>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.<h4>Methods</h4>Forty CR-Kp were genotyped by pulsed field gel electrophoresis, mul ...[more]

PMID: 24634498

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Project description:Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is recognized as a threat worldwide, but the mechanisms underlying its emergence remain unclear. As most CR-hvKP isolates are not hypermucoviscous, we speculated that the evolution of the capsule might result in the convergence of carbapenem resistance and hypervirulence. Here, 2,096 K. pneumoniae isolates were retrospectively collected to screen the ST23-K1 clone, and hypervirulence was roughly defined as being highly resistant to serum killing. The effect of wcaJ on the capsule, virulence, fitness, and resistance acquisition was further analyzed. The capsule gene wcaJ, inserted by ISKpn26/ISKpn74, was identified via whole-genome sequencing in four hvKP, but not hypermucoviscous, isolates. Uronic acid quantitation results revealed that these isolates produced significantly less capsular polysaccharides than NTUH-K2044. A significant increase in capsular production was observed in wcaJ-complemented isolates and confirmed by transmission electron microscopy. Further, all wcaJ-complemented isolates acquired greater resistance to macrophage phagocytosis, and one representative isolate resulted in a significantly higher mortality rate than the parental isolate in mice, indicating that wcaJ inactivation might compromise virulence. However, isolates with wcaJ interruption demonstrated a lower fitness cost and a high conjugation frequency of the blaKPC-2 plasmid, raising concerns about the emergence of carbapenem resistance in hvKP. IMPORTANCE Klebsiella pneumoniae is one of the most common nosocomial pathogens worldwide, and we speculated that the evolution of the capsule might result in the convergence of carbapenem resistance and hypervirulence of K. pneumoniae. The wcaJ gene was first reported to be interrupted by insertion sequence elements in ST23-K1 hypervirulent Klebsiella pneumoniae, resulting in little capsule synthesis, which plays an important role in virulence. We examined the effect of wcaJ on the capsule, virulence, and fitness. Isolates with wcaJ interruption might compromise virulence and demonstrated a lower fitness cost and a high conjugation frequency of the blaKPC-2 plasmid, highlighting its role as a potential factor facilitating hypervirulence and carbapenem resistance.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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