Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids

He, Shuhua; Chandler, Michaël; Varani, Alessandro M.; Hickman, A.B.; Dekker, John P.; Dyda, Fred

doi:10.1128/mbio.01987-16

Cited by 51 publications

(39 citation statements)

References 30 publications

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“…3B). Rearrangement of conjugation genes plays an important role in the dissemination of AMR genes between bacteria [21]. Because known IncR plasmids are non-transferable [22], an IncR plasmid carrying AMR genes, such as pMH17-012N_1, and another plasmid carrying conjugation genes, such as pMH17-012N_2, could be assumed to have been fused into a single plasmid with both AMR and conjugation genes, such as pMH13-051M_1, in a bacterium, and then been propagated by conjugation to another bacterium.…”

Section: Discussionmentioning

confidence: 99%

Plasmid analysis of NDM metallo-β-lactamase-producing Enterobacterales isolated in Vietnam

Hirabayashi

Yahara

Mitsuhashi

et al. 2020

Preprint

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24Carbapenem-resistant Enterobacteriaceae (CRE) represent a serious threat to public 25 health due to limited management of severe infections and high mortality. The rate of 26 resistance of Enterobacteriaceae isolates to major antimicrobials, including 27 carbapenems, is much higher in Vietnam than in Western countries, but the reasons 28 remain unknown due to the lack of genomic epidemiology research. A previous study 29 suggested that carbapenem resistance genes, such as the carbapenemase gene blaNDM-30 1, spread via plasmids among Enterobacteriaceae in Vietnam. In this study, we 31 performed detection and molecular characterization of blaNDM-1-carrying plasmids in CRE 32 isolated in Vietnam, and identified several possible cases of horizontal transfer of 33 plasmids both within and among species of bacteria. Twenty-five carbapenem-resistant 34 isolates from Enterobacteriaceae clinically isolated in a reference medical institution in 35Hanoi were sequenced on Illumina short-read sequencers, and 12 isolates harboring 36 blaNDM-1 were sequenced on an Oxford Nanopore Technologies long-read sequencer to 37 obtain complete plasmid sequences. Most of the plasmids co-carried genes conferring 38 resistance to clinically relevant antimicrobials, including third-generation cephalosporins, 39 aminoglycosides, and fluoroquinolones, in addition to blaNDM-1, leading to multidrug 40 resistance of their bacterial hosts. These results provide insight into the genetic basis of 41 CRE in Vietnam, and could help control nosocomial infections. 42 43

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Section: Discussionmentioning

confidence: 99%

Plasmid analysis of NDM metallo-β-lactamase-producing Enterobacterales isolated in Vietnam

Hirabayashi

Yahara

Mitsuhashi

et al. 2020

Preprint

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“…The presence of two copies of ISKpn25 on the chromosome and the plasmid suggested that the chromosomal insertion of the hsdMSR locus in mgrB was likely acquired from the plasmid through transposition or homologous recombination. Similarly, it has been suggested ISKpn25 is involved in DNA rearrangements among pKpQIL-like and possibly other plasmids (11). An additional study showed that a mobile element containing the carbapenemase OXA-181 disrupted the mgrB gene in a carbapenem-and colistin-resistant K. pneumoniae isolate from a patient from the United Arab Emirates (12).…”

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confidence: 92%

Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by Chromosomal Integration of Plasmid DNA

Cienfuegos-Gallet

Chen

Kreiswirth

et al. 2017

Antimicrob Agents Chemother

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Here we describe the spread of colistin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae in Medellín, Colombia. Among 32 isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB. Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25, indicating a clonal expansion of the resistant strain. The insertion region showed 100% identity to several plasmids, suggesting that the colistin resistance is mediated by chromosomal integration of plasmid DNA.

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“…Through sequence analysis, the backbone region of pWLK-KPC was found to be only a small part of the backbone regions of these 12 bla KPC -carrying plasmids. It is likely that pWLK-KPC is a trimmed-down version of a larger plasmid by homologous recombination, as exemplified by the findings by Conlan et al that pKPN-ff is a trimmed-down version of pKPN-498 31,32 . In addition, the comparison results by BRIG also showed that the bla KPC-2 -containing genetic structure in pWLK-KPC had been mobilized and inserted into different plasmids (purple rings, ring 34 to 37), indicating the high transmission capability of this region.…”

Section: Discussionmentioning

confidence: 99%

Coexistence of the blaNDM-1-carrying plasmid pWLK-NDM and the blaKPC-2-carrying plasmid pWLK-KPC in a Raoultella ornithinolytica isolate

Dang

Zhang

et al. 2020

Sci Rep

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coexistence of the bla NDM-1 -carrying plasmid pWLK-nDM and the bla KPC-2 -carrying plasmid pWLK-Kpc in a Raoultella ornithinolytica isolate to date, bla nDM and bla Kpc genes have been found predominantly in clinical settings around the world. in contrast, bacteria harbouring these two genes from natural environments are relatively less well studied compared to those found in clinical settings. in this study, a carbapenem-resistant Raoultella ornithinolytica strain, WLK218, was isolated from urban river sediment in Zhengzhou City, Henan province, china. this isolate was subjected to pcR and antimicrobial susceptibility testing. pcR results showed that this isolate was positive for both the bla NDM-1 and bla KPC-2 genes. the antimicrobial susceptibility testing results showed that this isolate exhibited resistance or intermediate resistance to all the antibiotics tested except for streptomycin (susceptible) and cefepime (susceptible-dose dependent). The complete genome sequence of the WLK218 isolate was then determined by using a combination of the pacBio and illumina sequencing technologies. the de novo assembly of the genome generated one chromosome and six plasmids. Among the six plasmids, the bla NDM-1 gene was carried on the IncX3 plasmid pWLK-NDM, while the bla KPC-2 gene was located on the untypeable plasmid pWLK-KPC. This is the first report of an environmental Raoultella ornithinolytica isolate co-harbouring the bla NDM-1 and bla KPC-2 genes.The increasing prevalence of multidrug-resistant Enterobacteriaceae pathogens has rendered life-saving antibiotics less effective, which has required clinicians to increasingly use last-resort antibiotics, such as carbapenems and polymyxins. However, the emergence and spread of antibiotic resistance genes (ARGs) conferring resistance to last-resort antibiotics have been observed across the globe in recent years, which has posed a challenging threat to public health 1-6 .As one of the ARGs conferring resistance to last-resort antibiotics, the bla NDM-1 gene has gained worldwide attention because the carbapenemase encoded by this gene can hydrolyse nearly all classes of β-lactams (including carbapenems), with the exception of monobactams 7 . The bla NDM-1 gene was first discovered in Klebsiella pneumoniae and Escherichia coli clinical isolates in India in 2008 8 . Just after the initial detection in clinical settings, bla NDM-1 -carrying isolates were soon found to be widely distributed in surface waters in the environment of New Delhi 9 . Since then, bla NDM genes have been extensively studied in clinical settings. Klebsiella pneumoniae carbapenemases (KPCs) are another type of carbapenemases which have also gained worldwide attention. The first member of KPC family, namely KPC-1, was identified in a Klebsiella pneumoniae clinical isolate in the USA in 1996 10 . Afterwards, KPC-producing bacteria have spread rapidly internationally, especially in China 11 . The situation of KPC in China is very serious. It is reported that China is one of the KPC endemic countries in ...

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Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids

Cited by 51 publications

References 30 publications

Plasmid analysis of NDM metallo-β-lactamase-producing Enterobacterales isolated in Vietnam

Plasmid analysis of NDM metallo-β-lactamase-producing Enterobacterales isolated in Vietnam

Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by Chromosomal Integration of Plasmid DNA

Coexistence of the blaNDM-1-carrying plasmid pWLK-NDM and the blaKPC-2-carrying plasmid pWLK-KPC in a Raoultella ornithinolytica isolate

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