title: Genetic structures at the origin of acquisition of the beta-lactamase bla KPC gene.
abstract: Genetic structures surrounding the carbapenem-hydrolyzing Ambler class A bla KPC gene were characterized in several KPC-positive Klebsiella pneumoniae and Pseudomonas aeruginosa strains isolated from the United States, Colombia, and Greece. The bla KPC genes were associated in all cases with transposon-related structures. In the K. pneumoniae YC isolate from the United States, the beta-lactamase bla KPC-2 gene was located on a novel Tn3-based transposon, Tn4401. Tn4401 was 10 kb in size, was delimited by two 39-bp imperfect inverted repeat sequences, and harbored, in addition to the beta-lactamase bla KPC-2 gene, a transposase gene, a resolvase gene, and two novel insertion sequences, ISKpn6 and ISKpn7. Tn4401 has been identified in all isolates. However, two isoforms of this transposon were found: Tn4401a was found in K. pneumoniae YC and K. pneumoniae GR from the United States and Greece, respectively, and differed by a 100-bp deletion, located just upstream of the bla KPC-2 gene, compared to the sequence of Tn4401b, which was found in the Colombian isolates. In all isolates tested, Tn4401 was flanked by a 5-bp target site duplication, the signature of a recent transposition event, and was inserted in different open reading frames located on plasmids that varied in size and nature. Tn4401 is likely at the origin of carbapenem-hydrolyzing beta-lactamase KPC mobilization to plasmids and its further insertion into various-sized plasmids identified in nonclonally related K. pneumoniae and P. aeruginosa isolates.
authors.affiliation: Service de Bactériologie-Virologie, INSERM U914: Emerging Resistance to Antibiotics, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre 94275, and Faculté de Médecine Paris-Sud, Paris, France. thierry.naas@bct.aphp.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Naas
authors.forename: Gaelle
authors.initials: G
authors.lastname: Cuzon
authors.forename: Maria-Virginia
authors.initials: MV
authors.lastname: Villegas
authors.forename: Marie-Frédérique
authors.initials: MF
authors.lastname: Lartigue
authors.forename: John P
authors.initials: JP
authors.lastname: Quinn
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D003105:Colombia; D004251:DNA Transposable Elements / Q000235:genetics*; D006115:Greece; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D014481:United States; D001618:beta-Lactamases / Q000235:genetics*; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D004251:DNA Transposable Elements; D047090:beta-Lactams; C491478:beta-lactamase KPC-2; D001618:beta-Lactamases