title: Dissemination of the blaKPC gene by clonal spread and horizontal gene transfer: comparative study of incidence and molecular mechanisms.
abstract: In addition to the global spread of the KPC-producing Klebsiella pneumoniae (KPC-KP) clonal complex (CC)-258 clone, the blaKPC gene may also spread by horizontal gene transfer (HGT), as suspected when more than one KPC-producing Enterobacteriaceae (KPC-Ent) species are isolated in a single patient. We aimed to characterize the incidence and molecular features of KPC-KP that were isolated alone (singular KPC-KP) versus KPC-KP that were isolated together with another KPC-Ent species (joint KPC-KP).
  
  
  
  Isolates were collected from April 2011 to August 2012 at the Laniado Medical Center. Typing was done by CC-258 multiplex PCR and MLST. Plasmids were characterized by plasmid MLST (pMLST). The genetic environment of the blaKPC gene was studied by sequencing.
  
  
  
  During the 17 month period, there were 281 cases of singular KPC-KP and 8 cases of joint KPC-KP (P < 0.0001). Among the patients with joint KPC-KP, the additional KPC-Ent species were Escherichia coli (n = 6), Enterobacter aerogenes (n = 1), Enterobacter cloacae (n = 1) and Citrobacter freundii (n = 1). All singular KPC-KP isolates tested (n = 27) belonged to the CC-258 clone and carried the blaKPC-3 allele, located inside a Tn4401a transposon. In contrast, joint KPC-KP/KPC-Ent isolates belonged to different STs and all but one carried the blaKPC-2 allele. The blaKPC-2 gene was located inside ΔTn4401c transposons that were harboured by IncN/pMLST ST-15-type plasmids possessing high conjugation efficiency.
  
  
  
  This study highlights two dissemination modes of the blaKPC gene: clonal spread of the CC-258 clone and, far less commonly, HGT-related spread, mediated by ST-15 plasmids that shuttle between a variety of species and clones.
authors.affiliation: National Center of Infection Control, Ministry of Health, Tel-Aviv, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel amosa@tlvmc.gov.il.
authors.forename: Amos
authors.initials: A
authors.lastname: Adler
authors.affiliation: National Center of Infection Control, Ministry of Health, Tel-Aviv, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Khabra
authors.affiliation: Department of Laboratories, Laniado Medical Center, Netanya, Israel.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Paikin
authors.affiliation: National Center of Infection Control, Ministry of Health, Tel-Aviv, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
mesh_terms: D004755:Enterobacteriaceae / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000453:epidemiology* / Q000382:microbiology*; D023061:Gene Order; D022761:Gene Transfer, Horizontal; D005798:Genes, Bacterial; D006801:Humans; D015994:Incidence; D058885:Multilocus Sequence Typing; D060885:Multiplex Polymerase Chain Reaction; D010957:Plasmids / Q000145:classification; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D001618:beta-Lactamases