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      Characterization of a novel bla NDM-5-harboring IncFII plasmid and an mcr-1-bearing IncI2 plasmid in a single Escherichia coli ST167 clinical isolate

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          Abstract

          Background and purpose

          The spread of the plasmid-mediated, colistin-resistance gene mcr-1 into New Delhi metallo-β-lactamase (NDM)-producing bacterial isolates can cause untreatable infections. In this study, we conducted a molecular characterization of a novel, conjugative, bla NDM-5-positive IncFII plasmid (pNDM-EC16-50) together with an mcr-1-bearing IncI2 plasmid in a single Escherichia coli ST167 clinical isolate EC16-50.

          Methods and results

          EC16-50, which belongs to the E. coli strain ST167 and phylogroup A, was identified to co-produce NDM-5 and MCR-1. S1-PFGE and Southern blotting showed that bla NDM-5 and mcr-1 genes were located oñ95 kb and ~65 kb plasmids, respectively. A conjugation assay revealed that both bla NDM-5- and mcr-1-bearing plasmids were self-transmissible. Comparative plasmid analysis suggested that bla NDM-5-harboring F2:A-:B-plasmid might have evolved from the well-reported NDM-carrying pMC-NDM-like plasmid via recombination with a locally emerged pSJ_94 plasmid, whereas the mcr-1-carrying IncI2 plasmid was similar to previously reported mcr-1-bearing plasmids in China.

          Conclusion and impact

          This study represents the first report of the NDM-5 carrying Inc-FII- but not IncX3-type plasmid in an MCR-1-producing E. coli isolate. More striking was the dissemination of mcr-1 in a successful epidemic NDM-5-producing E. coli clone ST167, which could facilitate the spread of colistin resistance in carbapenemase-producing E. coli isolates.

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          Most cited references27

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          Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network

          Carbapenem-resistant Enterobacteriaceae (CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible Citrobacter freundii , Escherichia coli , Enterobacter cloacae , or Klebsiella pneumoniae infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase gene identification were performed. Among 664 CRE cases, most were caused by K. pneumoniae (73.9%), followed by E. coli (16.6%) and E. cloacae (7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0 and differed significantly by region, with the highest in Jiangsu (14.97) and the lowest in Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients were male. Lower respiratory tract infections (65.4%) were the most common, followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed nonsusceptibility to carbapenems and cephalosporins. The susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher susceptibility rate against E. coli than against K. pneumoniae (90.9% versus 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases among K. pneumoniae and E. coli . The incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.
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            A Model for Transposition of the Colistin Resistance Gene mcr-1 by ISApl1.

            Analysis of mcr-1-containing sequences identified a common ∼2,607-bp DNA segment that in many cases is flanked on one or both ends by ISApl1 We present evidence that mcr-1 is mobilized by an ISApl1 composite transposon which has, in some cases, subsequently lost one or both copies of ISApl1 We also show that mcr-1 can be mobilized in some circumstances by a single upstream copy of ISApl1 in conjunction with the remnants of a downstream ISApl1.
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              Sharing more than friendship – transmission of NDM-5 ST167 and CTX-M-9 ST69 Escherichia coli between dogs and humans in a family, Finland, 2015

              Introduction Carbapenemase-producing Enterobacteriaceae (CPE) have rarely been reported in dogs, and never in animals in Finland. However, in April 2015, two meropenem-resistant Escherichia coli were identified from two dogs in one family. Both dogs suffered from chronic otitis externa. Methods: Epidemiological and molecular investigations (pulsed-field gel electrophoresis (PFGE), multilocus sequence typing) were conducted to investigate the source of infection and transmission routes. Results: In both dogs and one family member New Delhi metallo-beta-lactamase (NDM-5)-producing multidrug-resistant ST167 E. coli was found. Whole genome sequencing confirmed that the isolates were identical or only had one or two allelic differences. Additionally, the dogs and humans of the family carried an identical extended-spectrum beta-lactamase (ESBL) CTX-M-group 9 E. coli ST69 strain, indicating interspecies transmission. While the original source remains unclear, human-to-canine transmission is possible. No carbapenems had been administered to the dogs, but exposure to numerous other antimicrobials likely sustained the bacteria and supported its propagation in the canine host. Conclusion: To our knowledge, canine clinical NDM-5 E. coli in Europe, and confirmed CPE transmission between dogs and humans have not been previously reported. The screening of veterinary Enterobacteriaceae isolates for carbapenem resistance is highly recommended.
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                Author and article information

                Journal
                Infect Drug Resist
                Infect Drug Resist
                Infection and Drug Resistance
                Infection and Drug Resistance
                SAGE Publications (Sage UK: London, England )
                1178-6973
                2019
                01 March 2019
                : 12
                : 511-519
                Affiliations
                [1 ]The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China, xiewh1973@ 123456sina.com
                [2 ]School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China, qinshangshang@ 123456126.com
                [3 ]Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, Henan 450001, China, qinshangshang@ 123456126.com
                Author notes
                Correspondence: Shangshang Qin, School of Pharmaceutical Sciences, Zhengzhou University, Kexuedadao Road No.100, Zhengzhou, Henan 450001, China, Tel/Fax +86 371 6778 1895, Email qinshangshang@ 123456126.com
                Weihong Xie, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450001, China, Tel +86 371 6769 6508, Email xiewh1973@ 123456sina.com
                [*]

                These authors contributed equally to this work

                Article
                idr-12-511
                10.2147/IDR.S192998
                6402710
                30881056
                e4cced0d-6091-4d1b-94b2-8b45ac786583
                © 2019 Xu et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

                Infectious disease & Microbiology
                escherichia coli,st167,mcr-1,incfii plasmid,ndm-5
                Infectious disease & Microbiology
                escherichia coli, st167, mcr-1, incfii plasmid, ndm-5

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