Abstract
Klebsiella pneumoniae carbapenemase (KPC) actively hydrolyzes carbapenems, antibiotics often used a last-line treatment for multidrug-resistant bacteria. KPC clinical relevance resides in its widespread dissemination. In this work, we report the genomic context of KPC coding genes blaKPC-2, blaKPC-3 and blaKPC-30 in multidrug-resistant Klebsiella pneumoniae isolates from Brazil. Plasmids harboring blaKPC-3 and blaKPC-30 were identified. Fifteen additional carbapenem-resistant K. pneumoniae isolates were selected from the same tertiary hospital, collected over a period of 8 years. Their genomes were sequenced in order to evaluate the prevalence and dissemination of blaKPC–harboring plasmids. We found that blaKPC genes were mostly carried by one of two isoforms of transposon Tn4401 (Tn4401a or Tn4401b) that were predominantly located on plasmids highly similar to the previously described plasmid pKPC_FCF3SP (IncN). The identified pKPC_FCF3SP-like plasmids carried either blaKPC-2 or blaKPC-30. Two K. pneumoniae isolates harbored pKpQIL-like (IncFII) plasmids, only recently identified in Brazil; one of them harbored blaKPC-3 in a Tn4401a transposon. Underlining the risk of horizontal spread of KPC coding genes, this study reports the prevalence of blaKPC-2 and the recent spread of blaKPC-3, and blaKPC-30, in association with different isoforms of Tn4401, together with high synteny of plasmid backbones among isolates studied here and in comparison with previous reports.
Highlights
Infections caused by carbapenem-resistant Enterobacteriaceae represent a significant global health threat [1]
We looked for the genomic loci of the Klebsiella pneumoniae carbapenemase (KPC) genes; in all strains, the genes were located on contigs that were parts of plasmids (Figure 1B)
This is in agreement with previous observations, that is, the blaKPC gene is mostly carried by a multireplicon IncFIIk-IncFI plasmid [23,24]
Summary
Infections caused by carbapenem-resistant Enterobacteriaceae represent a significant global health threat [1]. There are three main groups of β-lactamases associated with resistance to carbapenems (carbapenemases): Klebsiella pneumoniae carbapenemase (KPC), metallo-βlactamases, and OXA-48-like β-lactamase. Mobile genetic elements, such as plasmids and transposons, are the main vectors enabling and facilitating the spread of these resistance determinants [3,4]. KPC is a plasmid-encoded enzyme which occurs in several different variants, and its clinical relevance is associated with its worldwide spread [5]. The treatment of infections by carbapenem-resistant Enterobacteriaceae is complicated, with severe clinical and socioeconomic consequences [4,17,18]
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