title: 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.
authors.affiliation: Department of Medicine Infectious Disease Division Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Diago-Navarro
authors.affiliation: Public Health Research Institute Tuberculosis Center, NJMS-Rutgers University, Newark, New Jersey.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institut Pasteur, Microbial Evolutionary Genomics CNRS, UMR3525, Paris, France;
authors.forename: Virginie
authors.initials: V
authors.lastname: Passet
authors.affiliation: Department of Medicine Infectious Disease Division Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York.
authors.forename: Seth
authors.initials: S
authors.lastname: Burack
authors.affiliation: Department of Medicine Infectious Disease Division Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York.
authors.forename: Amaia
authors.initials: A
authors.lastname: Ulacia-Hernando
authors.affiliation: Department of Medicine Infectious Disease Division Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York.
authors.forename: Rosy Priya
authors.initials: RP
authors.lastname: Kodiyanplakkal
authors.affiliation: Department of Clinical Microbiology Montefiore Medical Center, Bronx, New York.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Levi
authors.affiliation: Institut Pasteur, Microbial Evolutionary Genomics CNRS, UMR3525, Paris, France;
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brisse
authors.affiliation: Public Health Research Institute Tuberculosis Center, NJMS-Rutgers University, Newark, New Jersey.
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.affiliation: Department of Medicine Infectious Disease Division Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York.
authors.forename: Bettina C
authors.initials: BC
authors.lastname: Fries
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000907:Antibodies, Bacterial / Q000276:immunology; D016667:Bacterial Capsules / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D001770:Blood Bactericidal Activity; D015780:Carbapenems / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity*; D007915:Lepidoptera; D008264:Macrophages / Q000276:immunology; 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
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D015780:Carbapenems
keywords: Klebsiella pneumoniae; adjuvant therapy; carbapenem resistance; virulence