Carbapenem-resistant Klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits.
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.
['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|']
D000368:Aged D000369:Aged, 80 and over D000818:Animals D000900:Anti-Bacterial Agents D000907:Antibodies, Bacterial D016667:Bacterial Capsules D018441:Biofilms D001770:Blood Bactericidal Activity D015780:Carbapenems D005260:Female D005838:Genotype D006801:Humans D007710:Klebsiella Infections D007711:Klebsiella pneumoniae D007915:Lepidoptera D008264:Macrophages D008297:Male D008807:Mice, Inbred BALB C D008875:Middle Aged D058889:Molecular Typing D012189:Retrospective Studies D016019:Survival Analysis D014481:United States D014774:Virulence D018440:beta-Lactam Resistance
Klebsiella pneumoniae virulence adjuvant therapy carbapenem resistance