title: Quantification and comparison of virulence and characteristics of different variants of carbapenemase-producing Klebsiella pneumoniae clinical isolates from Taiwan and the United States.
abstract: OBJECTIVE
  The emergence of Klebsiella pneumoniae carbapenemase (KPC)-producing strains is a challenge for clinicians. The characteristics and virulence of variants of KPC-producing K. pneumoniae isolates were evaluated.
  
  
  METHODS
  Five clinical isolates-three KPC subtypes from Taiwan (KPC2-TW, KPC3-TW, and KPC17-TW) and two clinical strains from the United States (US; KPC2-US, KPC3-US)-were included. Virulent traits and capsular serotypes were analyzed by Polymerase Chain Reaction (PCR). Serum killing, neutrophil phagocytosis, and mice lethargy studies were performed to evaluate virulence.
  
  
  RESULTS
  Multilocus sequence typing (MLST) demonstrated that KPC2-TW and KPC17-TW belonged to sequence type (ST)11, and KPC2-US, KPC3-US, and KPC3-TW to ST258. KPC3-TW expressed capsular serotype K1, whereas the others were non-K1/K2/K5 isolates. MLST analysis indicated that ST11 strains were serum resistant, whereas ST258 isolates were serum sensitive. ST11 isolates exhibited significantly higher 15-minute phagocytic rates than ST258 isolates (70.28 ± 16.68% vs. 34.88 ± 10.52%, p < 0.001). The capsular serotype K1 strain was more resistant to neutrophil phagocytosis than non-K1/K2/K5 isolates (27.1 ± 10.23% vs. 54.46 ± 20.94%, p = 0.050). All KPC-producing strain variants from Taiwan and the US demonstrated less virulence in a mouse lethality study, where the LD50 ranged from approximately 10(6) colony-forming units (CFU) to >10(7) CFU. Immunological responses were not significantly correlated with KPC subtype; however, responses were associated with MLST and capsular serotype.
  
  
  CONCLUSIONS
  Production of KPC itself was not associated with increased virulence despite different variants of KPC. The ST11 KPC-producing strain was resistant to serum killing, whereas capsular ss K1 was associated with resistance to neutrophil phagocytosis.
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Tsung-Ta
authors.initials: TT
authors.lastname: Chiang
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ya-Sung
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Kuo-Ming
authors.initials: KM
authors.lastname: Yeh
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Sun-Kang
authors.initials: SK
authors.lastname: Chiu
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ning-Chi
authors.initials: NC
authors.lastname: Wang
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Te-Yu
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Division of Clinical Research, National Health Research Institutes, Taipei, Taiwan.
authors.forename: Li-Yueh
authors.initials: LY
authors.lastname: Huang
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Feng-Yee
authors.initials: FY
authors.lastname: Chang
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Division of Clinical Research, National Health Research Institutes, Taipei, Taiwan.
authors.forename: L K
authors.initials: LK
authors.lastname: Siu
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jung-Chung
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsinchu, Taiwan. Electronic address: jhchen@mail.ypu.edu.tw.
authors.forename: Jiun-Han
authors.initials: JH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology*; D001770:Blood Bactericidal Activity; D004195:Disease Models, Animal; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity*; D008807:Mice, Inbred BALB C; D058885:Multilocus Sequence Typing; D010587:Phagocytosis; D016133:Polymerase Chain Reaction; D012703:Serotyping; D013624:Taiwan; D014481:United States; D014774:Virulence; D037521:Virulence Factors / Q000032:analysis* / Q000235:genetics; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D037521:Virulence Factors; D001618:beta-Lactamases; C063912:carbapenemase
keywords: KPC variants; Klebsiella pneumoniae; virulence