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Antimicrobial Agents and Chemotherapy, April 2008, p. 1257-1263, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.01451-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Genetic Structures at the Origin of Acquisition of the β-Lactamase bla_KPC Gene

Thierry Naas,^1,* Gaelle Cuzon,^1, Maria-Virginia Villegas,² Marie-Frédérique Lartigue,¹ John P. Quinn,³ and Patrice Nordmann¹

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,¹ CIDEIM (International Center for Medical Research and Training), Cali, Colombia,² Stroger Hospital of Cook County and Chicago Infectious Disease Research Institute, Chicago, Illinois³

Received 8 November 2007/ Returned for modification 15 January 2008/ Accepted 21 January 2008

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 β-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 β-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 β-lactamase KPC mobilization to plasmids and its further insertion into various-sized plasmids identified in nonclonally related K. pneumoniae and P. aeruginosa isolates.

Published ahead of print on 28 January 2008.

T.N. and G.C. contributed equally to the work.

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