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Klebsiella pneumoniae multiresistance plasmid pMET1: similarity with the Yersinia pestis plasmid pCRY and integrative conjugative elements.

ABSTRACT: Dissemination of antimicrobial resistance genes has become an important public health and biodefense threat. Plasmids are important contributors to the rapid acquisition of antibiotic resistance by pathogenic bacteria.The nucleotide sequence of the Klebsiella pneumoniae multiresistance plasmid pMET1 comprises 41,723 bp and includes Tn1331.2, a transposon that carries the bla(TEM-1) gene and a perfect duplication of a 3-kbp region including the aac(6')-Ib, aadA1, and bla(OXA-9) genes. The replication region of pMET1 has been identified. Replication is independent of DNA polymerase I, and the replication region is highly related to that of the cryptic Yersinia pestis 91001 plasmid pCRY. The potential partition region has the general organization known as the parFG locus. The self-transmissible pMET1 plasmid includes a type IV secretion system consisting of proteins that make up the mating pair formation complex (Mpf) and the DNA transfer (Dtr) system. The Mpf is highly related to those in the plasmid pCRY, the mobilizable high-pathogenicity island from E. coli ECOR31 (HPI(ECOR31)), which has been proposed to be an integrative conjugative element (ICE) progenitor of high-pathogenicity islands in other Enterobacteriaceae including Yersinia species, and ICE(Kp1), an ICE found in a K. pneumoniae strain causing primary liver abscess. The Dtr MobB and MobC proteins are highly related to those of pCRY, but the endonuclease is related to that of plasmid pK245 and has no significant homology with the protein of similar function in pCRY. The region upstream of mobB includes the putative oriT and shares 90% identity with the same region in the HPI(ECOR31).The comparative analyses of pMET1 with pCRY, HPI(ECOR31), and ICE(Kp1 )show a very active rate of genetic exchanges between Enterobacteriaceae including Yersinia species, which represents a high public health and biodefense threat due to transfer of multiple resistance genes to pathogenic Yersinia strains.

SUBMITTER: Soler Bistue AJ

PROVIDER: S-EPMC2262945 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Klebsiella pneumoniae multiresistance plasmid pMET1: similarity with the Yersinia pestis plasmid pCRY and integrative conjugative elements.

Soler Bistué Alfonso J C AJ Birshan Daniel D Tomaras Andrew P AP Dandekar Manisha M Tran Tung T Newmark Jason J Bui Duyen D Gupta Nisha N Hernandez Keziah K Sarno Renee R Zorreguieta Angeles A Actis Luis A LA Tolmasky Marcelo E ME

PloS one 20080319 3

<h4>Background</h4>Dissemination of antimicrobial resistance genes has become an important public health and biodefense threat. Plasmids are important contributors to the rapid acquisition of antibiotic resistance by pathogenic bacteria.<h4>Principal findings</h4>The nucleotide sequence of the Klebsiella pneumoniae multiresistance plasmid pMET1 comprises 41,723 bp and includes Tn1331.2, a transposon that carries the bla(TEM-1) gene and a perfect duplication of a 3-kbp region including the aac(6' ...[more]

PMID: 18350140

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Project description:Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has received considerable attention. Typically, the genetic elements that confer virulence are harbored by nonconjugative plasmids. In this study, we report a CR-hvKP strain, CY814036, of high-risk sequence type 25 (ST25) and the K2 serotype, which is uncommon among K. pneumoniae isolates but caused serious lung infection in a tertiary teaching hospital in China. Whole-genome sequencing (WGS) revealed a rare conjugative plasmid, pCY814036-iucA, carrying a virulence-associated iuc operon (iucABCD-iutA) coding for aerobactin and determinants of multidrug resistance (MDR), coexisting with a conjugative blaKPC-2-bearing plasmid, pCY814036-KPC2, in the same strain. A conjugation assay showed that pCY814036-iucA and pCY814036-KPC2 could be efficiently cotransmitted from CY814036 to Escherichia coli EC600. Further phenotypic investigation, including antimicrobial susceptibility tests, serum resistance assays, and mouse infection models, confirmed that pCY814036-iucA was capable of cotransferring multidrug resistance and hypervirulence features to the recipient. pCY814036-KPC2 also conferred resistance to antibiotics, including β-lactams and aminoglycosides. Overall, the rare coexistence of a conjugative MDR-virulence plasmid and a blaKPC-2-bearing plasmid in a K. pneumoniae isolate offers a possible mechanism for the formation of CR-hvKP strains and the potential to significantly accelerate the propagation of high-risk phenotypes. IMPORTANCE The increased reporting of carbapenem-resistant hypervirulent K. pneumoniae is considered a worrisome concern to human health care and has restricted the choice of effective antibiotics for clinical treatment. Moreover, virulence plasmids with complete conjugation modules have been identified, which evolved via homologous recombination. Here, we characterize an ST25 CR-hvKP strain, CY814036, harboring both a conjugative MDR-virulence plasmid and a blaKPC-2-bearing plasmid in China. This study highlights that the cotransmission of drug resistance and virulence plasmids increases therapeutic difficulties and worsens clinical prognoses. Also, active surveillance of the conjugative MDR-virulence plasmid is necessary.

Dataset Information

Klebsiella pneumoniae multiresistance plasmid pMET1: similarity with the Yersinia pestis plasmid pCRY and integrative conjugative elements.

Publications

Klebsiella pneumoniae multiresistance plasmid pMET1: similarity with the Yersinia pestis plasmid pCRY and integrative conjugative elements.

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