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Genetic Structures at the Origin of Acquisition of the  Lactamase blaKPC Gene

Genetic Structures at the Origin of Acquisition of the  Lactamase blaKPC Gene,10.1128/AAC.01451-07,Antimicrobial Agents and Chemotherapy,Thierry Naas,

Genetic Structures at the Origin of Acquisition of the  Lactamase blaKPC Gene   (Citations: 38)
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Genetic structures surrounding the carbapenem-hydrolyzing Ambler class A blaKPC gene were characterized in several KPC-positive Klebsiella pneumoniae and Pseudomonas aeruginosa strains isolated from the United States, Colombia, and Greece. The blaKPC genes were associated in all cases with transposon-related struc- tures. In the K. pneumoniae YC isolate from the United States, the -lactamase blaKPC-2 gene was located on a novel Tn3-based transposon, Tn4401 .T n4401 was 10 kb in size, was delimited by two 39-bp imperfect inverted repeat sequences, and harbored, in addition to the -lactamase blaKPC-2 gene, a transposase gene, a resolvase gene, and two novel insertion sequences, ISKpn6 and ISKpn7 .T n4401 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 blaKPC-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 -lactamase KPC mobilization to plasmids and its further insertion into various-sized plasmids identified in nonclonally related K. pneumoniae and P. aeruginosa isolates.
Journal: Antimicrobial Agents and Chemotherapy - ANTIMICROB AGENTS CHEMOTHER , vol. 52, no. 4, pp. 1257-1263, 2008
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    • ...The putative β-lactamase genes were amplified and sequenced as described by Fiett et al. (2000) and Naas et al. (2008), respectively.Ampliconnucleotidesequencesweredetermined using an ABI PRISM 3130 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA) and analyzed by the BioEdit Sequence Alignment Editor and by BLASTn on the NCBI website (http://www.ncbi.nlm.nih.gov)...
    • ...The gene environment of blaKPC-2 was determined by polymerase chain reaction (PCR) mapping followed by amplicon sequencing as proposed by Naas et al. (2008)...

    Jaroslav Hrabáket al. KPC2-producing Klebsiella pneumoniae isolated from a Czech patient pre...

    • ...It was composed of ISKpn8 ,t heblaKPC-3 promoter, a 671-bp insertion, the blaKPC-3 gene and an ISkpn6-like element (Fig. 3). This DNA fragment is one part of a Tn3-based transposon, Tn4401, which is likely to be the origin of blaKPC mobilization and further insertion into various plasmids of non-clonally related organisms [10]...
    • ...This finding confirms Naas’s proposition [10] that this region of the element is unstable, and suggests that other isoforms of Tn4401 do exist...
    • ...Naas et al. identified a 100-bp deletion upstream of blaKPC from two clinical strains of K. pneumonia, namely, GR and YC [10]...

    G. Liet al. Novel genetic environment of the plasmid-mediated KPC3 gene detected i...

    • ...A study by Naas et al. (17) has described the association of blaKPC-2 with transposon Tn4401 on plasmids of various sizes from different organisms...
    • ...The flanking regions of the blaKPC genes sequenced thus far, excluding blaKPC-5, were related to Tn4401 (17)...

    Daniel J. Wolteret al. Phenotypic and Enzymatic Comparative Analysis of the Novel KPC Variant...

    • ...Recently, the genetic environment surrounding the blaKPC-2 gene on plasmids from three strains of K. pneumoniae and one of P. aeruginosa from diverse geographic sources was extensively characterized, identifying it as part of a 10-kb Tn3-based transposon designated Tn4401 (19)...
    • ...Tn4401a (containing the deletion) was identified in K. pneumoniae YC and K. pneumoniae GR isolated from the United States and Greece, respectively (19), while isoform Tn4401b (lacking the deletion) was identified from a K. pneumoniae strain and a P. aeruginosa strain isolated from Colombia (19)...
    • ...Tn4401a (containing the deletion) was identified in K. pneumoniae YC and K. pneumoniae GR isolated from the United States and Greece, respectively (19), while isoform Tn4401b (lacking the deletion) was identified from a K. pneumoniae strain and a P. aeruginosa strain isolated from Colombia (19)...
    • ...This element was designated Tn4401 by Naas et al. (19) and has been found entirely or in part in all of the blaKPC sequences so far deposited in GenBank...
    • ...A comparison of the 10-kb Tn4401 element found in the 15 strains we studied with those deposited in EMBL/GenBank (accession numbers EU176011 to EU176014) indicated that this Tn3-related element existed as two distinct isoforms differing by a 100-bp deletion occurring at nucleotide 7666 according to sequence accession number EU176012 (19)...
    • ...As shown in Table 2, 10/15 of the elements carried this deletion and were classified as Tn4401a following the designation of Naas et al. (19)...
    • ...While genetic information for the strains in this study was presented in early 2008 (17), a subsequent study detailing the genetic environment surrounding the KPC gene was published describing the common 10-kb element Tn4401 (19)...
    • ...As in a recently reported case (19), one of the current strains (S15) contained the KPC gene on two different plasmids, reflecting the ability of the gene to mobilize to different species of DNA in a cell...
    • ...Naas et al. (19) identified the 100-bp deletion in this region from two clinical strains of K. pneumoniae, GR and YC, isolated from Greece and the United States, respectively, and they point out that another KPC sequence deposited in GenBank (DQ989640) contains a 200-bp deletion in this area...
    • ...by on March 3, 2010 aac.asm.org Downloaded from Our results, together with those of Naas et al. (19), provide important information regarding the active evolution of plasmid-carried KPC carbapenemase genes as part of two isoforms of Tn4401...

    Thomas D. Gootzet al. Genetic Organization of Transposase Regions Surrounding blaKPC Carbape...

    • ...However, the spread of blaKPC into different genera is most likely associated with its residence within mobile genetic elements on plasmids of various sizes (14)...

    Daniel J. Wolteret al. Surveillance of Carbapenem-Resistant Pseudomonas aeruginosa Isolates f...

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