NDM-1 encoded by a pNDM-HN380-like plasmid pNDM-BJ03 in clinical Enterobacter cloacae

Lü, Yang; Liu, Wei; Liang, Hui; Zhao, Shulong; Zhang, Wei; Liu, Jia; Jin, Cheng; Hu, Hongbo

doi:10.1016/j.diagmicrobio.2017.10.022

Cited by 6 publications

(4 citation statements)

References 20 publications

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“…This is an important finding. However, even more importantly, our BLASTn analysis showed that IncX3 plasmids harboring various bla NDM genes, including bla NDM–1 (Lü et al, 2018; Zhu et al, 2018), bla NDM–4 (Espedido et al, 2015; Sugawara et al, 2017), bla NDM–5 (Krishnaraju et al, 2015; Zhu et al, 2016; Li et al, 2018; Xie et al, 2018) , bla NDM–6, bla NDM–7 (Pal et al, 2017; Sugawara et al, 2017), bla NDM–13 (Lv et al, 2016), bla NDM–17 (Liu et al, 2017), bla NDM–19 (Liu et al, 2019), bla NDM–20 (Liu Z. et al, 2018), and bla NDM–21 (Liu L. et al, 2018), which have been found in 15 species among Enterobacterales [ K. pneumoniae (Espedido et al, 2015; Krishnaraju et al, 2015) , K. oxytoca (Paskova et al, 2018; Yoon et al, 2018), Klebsiella michiganensis, Klebsiella aerogenes, E. coli (Zhu et al, 2016; Pal et al, 2017; Sugawara et al, 2017; Li et al, 2018; Xie et al, 2018) , C. freundii (Zhu et al, 2018) , S. enteric, Enterobacter hormaechei, Enterobacter cloacae (Lü et al, 2018) , Enterobacter asburiae (Paskova et al, 2018) , Enterobacter xiangfangensis (Paskova et al, 2018) , Cronobacter sakazakii, Raoultella planticola, Raoultella ornithinolytica (Paskova et al, 2018), and Kluyvera intermedia (Paskova et al, 2018)] from 13 different countries around the world thus far. These countries are China (Zhu et al, 2016; Li et al, 2018; Liu Z. et al, 2018; Xie et al, 2018), the Czech Republic (Paskova et al, 2018), Kuwait (Pal et al, 2017), Korea (Yoon et al, 2018), Oman (Pal et al, 2017), United States, Sweden, Myanmar (Sugawara et al, 2017), Vietnam, India (Krishnaraju et al, 2015), Arabian Peninsula (Pal et al, 2017), Canada, and Australia (Espedido et al, 2015).…”

Section: Discussionmentioning

confidence: 92%

Detection and Genomic Characterization of a Morganella morganii Isolate From China That Produces NDM-5

et al. 2019

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The increasing prevalence and transmission of the carbapenem resistance gene bla NDM–5 has led to a severe threat to public health. So far, bla NDM–5 has been widely detected in various species of Enterobacterales and different hosts across various cities. However, there is no report on the bla NDM–5– harboring Morganella morganii. In January 2016, the first NDM-5-producing Morganella morganii L241 was found in a stool sample of a patient diagnosed as recurrence of liver cancer in China. Identification of the species was performed using 16S rRNA gene sequencing. Carbapenemase genes were identified through both PCR and sequencing. To investigate the characteristics and complete genome sequence of the bla NDM–5 -harboring clinical isolate, antimicrobial susceptibility testing, S1 nuclease pulsed field gel electrophoresis, Southern blotting, transconjugation experiment, complete genome sequencing, and comparative genomic analysis were performed. M. morganii L241 was found to be resistant to broad-spectrum cephalosporins and carbapenems. The complete genome of L241 is made up from both a 3,850,444 bp circular chromosome and a 46,161 bp self-transmissible IncX3 plasmid encoding bla NDM–5 , which shared a conserved genetic context of bla NDM–5 (ΔIS 3000 -ΔIS Aba125 -IS 5 - bla NDM–5 - ble - trpF - dsbC -IS 26 ). BLASTn analysis showed that IncX3 plasmids harboring bla NDM genes have been found in 15 species among Enterobacterales from 13 different countries around the world thus far. In addition, comparative genomic analysis showed that M. morganii L241 exhibits a close relationship to M. morganii subsp. morganii KT with 107 SNPs. Our research demonstrated that IncX3 is a key element in the worldwide dissemination of bla NDM - 5 among various species. Further research will be necessary to control and prevent the spread of such plasmids.

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Section: Discussionmentioning

confidence: 92%

Detection and Genomic Characterization of a Morganella morganii Isolate From China That Produces NDM-5

et al. 2019

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“…The direct spread of NDM-1 or NDM-5 by IncX3-type plasmids among Enterobacteriaceae was very common in China. 30,31 Here, the pE648NDM-5 has 96% identity with the other two plasmids, the pNDM5_IncX3 (GenBank ID KU761328) isolated from a clinical K. pneumoniae and the pP855-NDM5 (GenBank ID MF547508) in an E. coli ST7511 strain isolated from a pig, 3,31 as shown in Figure 4; indicating the epidemicity of bla NDM-5 -carrying IncX3 plasmids among Enterobacteriaceae.…”

Section: Overview and Comparative Analysis Of Pe648ndm-5 And Pe648mcr-1mentioning

confidence: 95%

A Novel blaCTX-M-65-Harboring IncHI2 Plasmid pE648CTX-M-65 Isolated from a Clinical Extensively-Drug-Resistant Escherichia coli ST648

Lü

Kang²,

Fan³

2020

IDR

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Background: An ESBL, carbapenemase-and MCR-1-producing Escherichia coli ST648 strain was isolated from the urine sample of a patient in a Chinese tertiary hospital in 2016. Methods: The strain was fully sequenced by GridION X5 platform of Oxford Nanopore Technology. Results: The sequence analysis showed that the extended-spectrum β-lactamases CTX-M-65 and OXA-1, the carbapenemase NDM-5, the MCR-1 were encoded, respectively, by three different resistance plasmids. The pE648CTX-M-65-carrying bla CTX-M-65 was a novel conjugative plasmid belonging to IncHI2 type; except for the bla CTX-M-65 , it also carried resistance genes ble, floR, sul1, aph(4)-Ia, aac(3)-VI, aac(6ʹ)-II, bla OXA-1 , catB, arr3 and tetA. Besides, an IncX4 plasmid pE648MCR-1-carrying mcr-1 and an IncX3 plasmid pE648NDM-5-carrying bla NDM-5 were also identified. Conclusion: The three transferable resistance plasmids coexisting in the E. coli ST648 isolate indicated the high risk to disseminate the extensively-drug-resistance among Enterobacteriaceae.

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“…Although a number of promising inhibitor molecules have been reported in recent years, there are no effective inhibitors against MβLs available for clinical therapy [8]. More seriously, new Delphi metallo-β-lactamase 1 (NDM-1), which were first identified from pathogenic bacterium in 2008 and classified as B1 subclass MβLs, greatly aggravates the challenge to treat bacterial infection in clinic because of the ability to hydrolyze almost all β-lactam antibiotics [9,10,11]. Obviously, lack of knowledge about catalytic mechanisms of NDM-1 has delayed the development of clinical inhibitors [12].…”

Section: Introductionmentioning

confidence: 99%

Halogen-Substituted Triazolethioacetamides as a Potent Skeleton for the Development of Metallo-β-Lactamase Inhibitors

et al. 2019

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Metallo-β-lactamases (MβLs) are the target enzymes of β-lactam antibiotic resistance, and there are no effective inhibitors against MβLs available for clinic so far. In this study, thirteen halogen-substituted triazolethioacetamides were designed and synthesized as a potent skeleton of MβLs inhibitors. All the compounds displayed inhibitory activity against ImiS with an IC50 value range of 0.032–15.64 μM except 7. The chlorine substituted compounds (1, 2 and 3) inhibited NDM-1 with an IC50 value of less than 0.96 μM, and the fluorine substituted 12 and 13 inhibited VIM-2 with IC50 values of 38.9 and 2.8 μM, respectively. However, none of the triazolethioacetamides exhibited activity against L1 at inhibitor concentrations of up to 1 mM. Enzyme inhibition kinetics revealed that 9 and 13 are mixed inhibitors for ImiS with Ki values of 0.074 and 0.27μM using imipenem as the substrate. Docking studies showed that 1 and 9, which have the highest inhibitory activity against ImiS, fit the binding site of CphA as a replacement of ImiS via stable interactions between the triazole group bridging ASP120 and hydroxyl group bridging ASN233.

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NDM-1 encoded by a pNDM-HN380-like plasmid pNDM-BJ03 in clinical Enterobacter cloacae

Cited by 6 publications

References 20 publications

Detection and Genomic Characterization of a Morganella morganii Isolate From China That Produces NDM-5

Detection and Genomic Characterization of a Morganella morganii Isolate From China That Produces NDM-5

<p>A Novel <em>bla</em><sub>CTX-M-65</sub>-Harboring IncHI2 Plasmid pE648CTX-M-65 Isolated from a Clinical Extensively-Drug-Resistant <em>Escherichia coli</em> ST648</p>

Halogen-Substituted Triazolethioacetamides as a Potent Skeleton for the Development of Metallo-β-Lactamase Inhibitors

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