Carbapenem-Resistant Klebsiella pneumoniae Exhibit Variability in Capsular Polysaccharide and Capsule Associated Virulence Traits
E Diago-Navarro, L Chen, V Passet… - The Journal of …, 2014 - academic.oup.com
E Diago-Navarro, L Chen, V Passet, S Burack, A Ulacia-Hernando, RP Kodiyanplakkal…
The Journal of infectious diseases, 2014•academic.oup.comBackground. 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 …
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 …
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.
Oxford University Press