title: Resistance to carbapenems in sequence type 11 Klebsiella pneumoniae is related to DHA-1 and loss of OmpK35 and/or OmpK36.
abstract: This study investigated the molecular mechanisms of carbapenem resistance in clinical isolates of Klebsiella pneumoniae from Korea and the clinical outcomes of resistant K. pneumoniae infection. Sixteen K. pneumoniae isolates showing resistance to carbapenems collected from a tertiary-care hospital were examined for the mechanisms of carbapenem resistance. PCR and sequencing experiments detected the bla(DHA-1) AmpC β-lactamase gene in all 16 clinical isolates, whilst the bla genes of extended-spectrum β-lactamases were detected in 12 of 16 isolates. SDS-PAGE experiments indicated that all the isolates lacked the 35 kDa and/or 36 kDa outer-membrane proteins (OMPs). Sequence analysis of the corresponding OMP genes revealed various alterations. PFGE analysis demonstrated that there were no major clonal relationships among the K. pneumoniae isolates. However, multilocus sequence typing experiments showed that all isolates shared the same sequence type (ST), ST11, except for one isolate of ST48. The crude mortality rate of infected patients was 81.8 %. Carbapenem resistance was mainly due to a combination of DHA-1 AmpC β-lactamase coupled with the loss of OmpK35 and/or OmpK36 and was associated with poor clinical outcome.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: So Youn
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Il Kwon
authors.initials: IK
authors.lastname: Bae
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Juwon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Seok Hoon
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Yong
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: June Myung
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyungwon
authors.initials: K
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000032:analysis; D015780:Carbapenems / Q000494:pharmacology*; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005838:Genotype; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology* / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000737:chemistry / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D016133:Polymerase Chain Reaction; D018272:Porins / Q000032:analysis / Q000172:deficiency*; D020543:Proteome / Q000032:analysis; D056910:Republic of Korea; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D004269:DNA, Bacterial; C119261:OmpK35 porin, Klebsiella pneumoniae; C092233:OmpK36 protein, Klebsiella pneumoniae; D018272:Porins; D020543:Proteome