TY - JOUR
T1 - Carbapenem-resistant klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits
AU - Diago-Navarro, Elizabeth
AU - Chen, Liang
AU - Passet, Virginie
AU - Burack, Seth
AU - Ulacia-Hernando, Amaia
AU - Kodiyanplakkal, Rosy Priya
AU - Levi, Michael H.
AU - Brisse, Sylvain
AU - Kreiswirth, Barry N.
AU - Fries, Bettina C.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - Background. Novel therapies are urgently needed to treat carbapenem-resistant Klebsiella pneumoniae (CRKp)- 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 coimmunization 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.
AB - Background. Novel therapies are urgently needed to treat carbapenem-resistant Klebsiella pneumoniae (CRKp)- 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 coimmunization 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.
KW - Adjuvant therapy
KW - Carbapenem resistance
KW - Klebsiella pneumoniae
KW - Virulence
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U2 - 10.1093/infdis/jiu157
DO - 10.1093/infdis/jiu157
M3 - Article
C2 - 24634498
AN - SCOPUS:84901282068
SN - 0022-1899
VL - 210
SP - 803
EP - 813
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 5
ER -