A Cointegrate-Like Plasmid That Facilitates Dissemination by Conjugation of the Extended-Spectrum β-Lactamase CTX-M-17

Lin, David L.; Ramírez, María Soledad; Tran, Tung; Tolmasky, Marcelo E.

doi:10.1128/aac.01365-13

Cited by 11 publications

(9 citation statements)

References 12 publications

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“…Additionally, the creation of a multireplicon plasmid broadens its host range by overcoming the incompatibility due to the presence of a single resident plasmid (5). Our study and data from others suggest that plasmid cointegration may significantly facilitate the spread of antimicrobial resistance genes (7,20,21) as well as of other determinants that have clinical impact.…”

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confidence: 54%

Complete Sequence of a bla _KPC -Harboring Cointegrate Plasmid Isolated from Escherichia coli

Chavda

Chen

Jacobs

et al. 2015

Antimicrob Agents Chemother

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e Horizontal transfer of bla KPC -harboring plasmids contributes significantly to the inter-and intraspecies spread of Klebsiella pneumoniae carbapenemase (KPC). Here we report the complete nucleotide sequence of a bla KPC -harboring IncFIA plasmid, pBK32533, from Escherichia coli. pBK32533 is a cointegrate plasmid comprising of a 72-kb sequence identical to that of the nonconjugative pBK30661 plasmid plus an additional 170-kb element that harbors the genes for plasmid transfer. pBK32533 demonstrates how bla KPC can be spread from a nonconjugative plasmid through cointegration.T he rapid emergence of carbapenem resistance in pathogenic Gram-negative bacteria (GNB) is a major global concern. The increasing incidence and spread of Klebsiella pneumoniae carbapenemase (KPC) have been well documented among nosocomial K. pneumoniae infections in the northeastern United States (1, 2). Two scenarios contribute to the spread of these emerging pathogens which challenge the design of effective infection control strategies. First, there is dispersion of KPC-harboring strains from well-established backgrounds-clonal dissemination (1, 2). For example, KPC has successfully disseminated worldwide, and the dissemination is mostly attributed to a K. pneumoniae clone, ST258 (2, 3). Second, strains become resistant as a consequence of de novo acquisition of bla KPC -harboring plasmids (4). The interand intraspecies dissemination of bla KPC is made possible by its presence on various bla KPC -harboring transferable plasmids. Currently, a wide range of KPC plasmids with different incompatibility (Inc) replicon groups, including IncFIA, IncFII, IncN, IncX, IncR, IncI2, IncA/C, ColE1, and IncL/M, have been identified (2). The importance of these varied genetic backbones has been reviewed recently (2).IncF plasmids are a large family of low-copy-number plasmids and are primarily restricted to the family of Enterobacteriaceae (5). Plasmids belonging to IncF family are linked to the emergence of resistance to ␤-lactam antibiotics worldwide, including carbapenem resistance (5-8). Among them, bla KPC -harboring IncFIA plasmids are widely distributed in parts of the northeastern United States (7). In a recent molecular surveillance study, we found two bla KPC -harboring IncFIA plasmids, pBK30661 and pBK30683, accounting for ϳ20% of the KPC-producing isolates in 10 hospitals in New York and New Jersey (7). Among them, pBK30661 is nonconjugative and harbors multiple antimicrobial resistance determinants but lacks the plasmid transfer operon (tra) and the origin of transfer site (oriT) regions (7). In contrast, pBK30683 carries a nearly identical pBK30661-like region as well as an additional 68-kb fragment harboring the tra and oriT elements (7). To determine the significance of this finding, we designed four duplex PCRs using plasmid markers to detect plasmids similar to pBK30661 and pBK30683 in a collection of KPCcarrying Enterobacteriaceae isolates (7). Intriguingly, pBK30661-like plasmids (determined by pBK30661 PCR-specific markers) were f...

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confidence: 54%

Complete Sequence of a bla _KPC -Harboring Cointegrate Plasmid Isolated from Escherichia coli

Chavda

Chen

Jacobs

et al. 2015

Antimicrob Agents Chemother

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“…This novel cointegrated plasmid, pBK30683, therefore acquired the ability to transfer by conjugation, facilitating dissemination of carbapenem resistance among different strains and species. Plasmid cointegration is not rare in Gram-negative or Gram-positive bacteria and has been associated with the spread of antimicrobial resistance genes, including genes for ␤-lactamases (30,31). For example, Lin et al recently reported the cointegration of a nonconjugative bla CTX-M-17 -bearing plasmid, pIP843, with an ϳ73-kb conjugative plasmid that may be responsible for the spread of CTX-M-17 (31).…”

Section: Discussionmentioning

confidence: 99%

Molecular Survey of the Dissemination of Two bla _KPC -Harboring IncFIA Plasmids in New Jersey and New York Hospitals

Chen

Chavda

Melano

et al. 2014

Antimicrob Agents Chemother

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i Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains have spread worldwide and become a major threat in health care facilities. Transmission of bla KPC , the plasmid-borne KPC gene, can be mediated by clonal spread and horizontal transfer. Here, we report the complete nucleotide sequences of two novel bla KPC-3 -harboring IncFIA plasmids, pBK30661 and pBK30683. pBK30661 is 74 kb in length, with a mosaic plasmid structure; it exhibits homologies to several other plasmids but lacks the plasmid transfer operon (tra) and the origin of transfer (oriT) that are required for plasmid transfer. pBK30683 is a conjugative plasmid with a cointegrated plasmid structure, comprising a 72-kb element that highly resembles pBK30661 (>99.9% nucleotide identities) and an extra 68-kb element that harbors tra and oriT. A PCR scheme was designed to detect the distribution of bla KPC -harboring IncFIA (pBK30661-like and pBK30683-like) plasmids in a collection of clinical Enterobacteriaceae isolates from 10 hospitals in New Jersey and New York. KPC-harboring IncFIA plasmids were found in 20% of 491 K. pneumoniae isolates, and all carried bla KPC-3 . pBK30661-like plasmids were identified mainly in the epidemic sequence type 258 (ST258) K. pneumoniae clone, while pBK30683-like plasmids were widely distributed in ST258 and other K. pneumoniae sequence types and among non-K. pneumoniae Enterobacteriaceae species. This suggests that both clonal spread and horizontal plasmid transfer contributed to the dissemination of bla KPC -harboring IncFIA plasmids in our area. Further studies are needed to understand the distribution of this plasmid group in other health care regions and to decipher the origins of pBK30661-like and pBK30683-like plasmids.

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“…However, although carrying a more modest number of genes, small high-copy number plasmids are of interest because they have a significant impact on bacterial infection harboring a variety of resistance genes that are expressed at high levels and that are usually included in mobile elements. These plasmids also play important, albeit still understudied, roles in plasmid evolution through events mediated by mobile elements as well as several recombinational mechanisms of cointegration with other plasmids that can be followed by imprecise resolution (Zakharova et al, 2002; Bui et al, 2006; Tran et al, 2012; Lin et al, 2013; Ramirez et al, 2014a; He et al, 2015; Cameranesi et al, 2018). Recent studies also showed that multicopy plasmids promote evolution by permitting the coexistence of novel and ancestral traits when a new variant arises through mutation, allowing bacteria to escape the evolutionary constraints imposed by the trade-offs that otherwise would limit the perpetuation of certain gene changes (Rodriguez-Beltran et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Small Klebsiella pneumoniae Plasmids: Neglected Contributors to Antibiotic Resistance

et al. 2019

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Klebsiella pneumoniae is the causative agent of community-and, more commonly, hospital-acquired infections. Infections caused by this bacterium have recently become more dangerous due to the acquisition of multiresistance to antibiotics and the rise of hypervirulent variants. Plasmids usually carry genes coding for resistance to antibiotics or virulence factors, and the recent sequence of complete K. pneumoniae genomes showed that most strains harbor many of them. Unlike large plasmids, small, usually high copy number plasmids, did not attract much attention. However, these plasmids may include genes coding for specialized functions, such as antibiotic resistance, that can be expressed at high levels due to gene dosage effect. These genes may be part of mobile elements that not only facilitate their dissemination but also participate in plasmid evolution. Furthermore, high copy number plasmids may also play a role in evolution by allowing coexistence of mutated and non-mutated versions of a gene, which helps to circumvent the constraints imposed by trade-offs after certain genes mutate. Most K. pneumoniae plasmids 25-kb or smaller replicate by the ColE1-type mechanism and many of them are mobilizable. The transposon Tn1331 and derivatives were found in a high percentage of these plasmids. Another transposon that was found in representatives of this group is the bla KPC-containing Tn4401. Common resistance determinants found in these plasmids were aac(6)-Ib and genes coding for β-lactamases including carbapenemases.

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A Cointegrate-Like Plasmid That Facilitates Dissemination by Conjugation of the Extended-Spectrum β-Lactamase CTX-M-17

Cited by 11 publications

References 12 publications

Complete Sequence of a bla _KPC -Harboring Cointegrate Plasmid Isolated from Escherichia coli

Complete Sequence of a bla _KPC -Harboring Cointegrate Plasmid Isolated from Escherichia coli

Molecular Survey of the Dissemination of Two bla _KPC -Harboring IncFIA Plasmids in New Jersey and New York Hospitals

Small Klebsiella pneumoniae Plasmids: Neglected Contributors to Antibiotic Resistance

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A Cointegrate-Like Plasmid That Facilitates Dissemination by Conjugation of the Extended-Spectrum β-Lactamase CTX-M-17

Cited by 11 publications

References 12 publications

Complete Sequence of a bla KPC -Harboring Cointegrate Plasmid Isolated from Escherichia coli

Complete Sequence of a bla KPC -Harboring Cointegrate Plasmid Isolated from Escherichia coli

Molecular Survey of the Dissemination of Two bla KPC -Harboring IncFIA Plasmids in New Jersey and New York Hospitals

Small Klebsiella pneumoniae Plasmids: Neglected Contributors to Antibiotic Resistance

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Complete Sequence of a bla _KPC -Harboring Cointegrate Plasmid Isolated from Escherichia coli

Complete Sequence of a bla _KPC -Harboring Cointegrate Plasmid Isolated from Escherichia coli

Molecular Survey of the Dissemination of Two bla _KPC -Harboring IncFIA Plasmids in New Jersey and New York Hospitals