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      High Prevalence of bla NDM Variants Among Carbapenem-Resistant Escherichia coli in Northern Jiangsu Province, China

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          Abstract

          The continuous emergence of carbapenem-resistant Escherichia coli (CRECO) presents a great challenge to public health. New Delhi metallo-lactamase (NDM) variants are widely disseminated in China, so the research on the prevalence and transmission of diverse bla NDM variants is urgently needed. In the present study, 54 CRECO isolates were collected from 1,185 Escherichia coli isolates in five hospitals in Northern Jiangsu Province, China from September 2015 to August 2016. Antimicrobial susceptibility tests, PCR detection of resistance determinants, multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to characterize these strains. Plasmid conjugation experiments were carried out to determine the transferability of resistant genes from selected isolates. PCR-based replicon typing (PBRT), S1 nuclease-PFGE, and Southern blotting were conducted for plasmid profiling. Carbapenemase genes were detectable in all CRECO isolates, among which thirty-one CRECO isolates were found to carry bla NDM−5 (54.7%), while, bla NDM−1, bla NDM−7, bla NDM−4, bla NDM−9, and bla KPC−2 were identified in 14, five, two, one, and one isolates, respectively. MLST results revealed 15 different STs and four new STs were first reported to be linked with NDM-producing isolates. PFGE typing showed that no more than two isolates with the same ST appeared to the same band pattern except three ST410 isolates. Twenty-six selected NDM-producing isolates were successfully transferred to E. coli J53 by conjugation experiments. Notably, 50.0% (13/26) of bla NDM variants were found to be carried by ~55 kb IncX3 plasmid. Our study reported a high prevalence of bla NDM variants, especially bla NDM−5, in Northern Jiangsu province, China. Diverse bla NDM variants were mainly carried by ~55 kb IncX3 plasmids, suggesting that the fast evolution and high transferability of this kind of plasmid promote the high prevalence of bla NDM variants. Therefore, large-scale surveillance and effective infection control measures are also urgently needed to prevent diverse bla NDM variants from becoming epidemic in the future.

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          The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide.

          The spread of carbapenemase producers in Enterobacteriaceae has now been identified worldwide. Three main carbapenemases have been reported; they belong to three classes of β-lactamases, which are KPC, NDM, and OXA-48. The main reservoirs of KPC are Klebsiella pneumoniae in the USA, Israel, Greece, and Italy, those of NDM are K. pneumoniae and Escherichia coli in the Indian subcontinent, and those of OXA-48 are K. pneumoniae and Escherichia coli in North Africa and Turkey. KPC producers have been mostly identified among nosocomial isolates, whereas NDM and OXA-48 producers are both nosocomial and community-acquired pathogens. Control of their spread is still possible in hospital settings, and relies on the use of rapid diagnostic techniques and the strict implemention of hygiene measures.
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            Structure, Genetics and Worldwide Spread of New Delhi Metallo-β-lactamase (NDM): a threat to public health

            Background The emergence of carbapenemase producing bacteria, especially New Delhi metallo-β-lactamase (NDM-1) and its variants, worldwide, has raised amajor public health concern. NDM-1 hydrolyzes a wide range of β-lactam antibiotics, including carbapenems, which are the last resort of antibiotics for the treatment of infections caused by resistant strain of bacteria. Main body In this review, we have discussed bla NDM-1variants, its genetic analysis including type of specific mutation, origin of country and spread among several type of bacterial species. Wide members of enterobacteriaceae, most commonly Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and gram-negative non-fermenters Pseudomonas spp. and Acinetobacter baumannii were found to carry these markers. Moreover, at least seventeen variants of bla NDM-type gene differing into one or two residues of amino acids at distinct positions have been reported so far among different species of bacteria from different countries. The genetic and structural studies of these variants are important to understand the mechanism of antibiotic hydrolysis as well as to design new molecules with inhibitory activity against antibiotics. Conclusion This review provides a comprehensive view of structural differences among NDM-1 variants, which are a driving force behind their spread across the globe. Electronic supplementary material The online version of this article (doi:10.1186/s12866-017-1012-8) contains supplementary material, which is available to authorized users.
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              Detection of Plasmid-Mediated AmpC  -Lactamase Genes in Clinical Isolates by Using Multiplex PCR

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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                13 November 2018
                2018
                : 9
                : 2704
                Affiliations
                [1] 1Medical Technology School, Xuzhou Medical University , Xuzhou, China
                [2] 2Jiangsu Provincial Center for Disease Control and Prevention , Nanjing, China
                [3] 3Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University , Xuzhou, China
                Author notes

                Edited by: Liang Chen, Public Health Research Institute (PHRI), United States

                Reviewed by: Jian-Hua Liu, South China Agricultural University, China; Kalyan Chavda, Rutgers, The State University of New Jersey, Newark, United States

                *Correspondence: Bing Gu gb20031129@ 123456163.com

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                †Present Address: Ruru Bi, Department of Laboratory Medicine, Suzhou Science and Technology Town Hospital, Suzhou, China

                Article
                10.3389/fmicb.2018.02704
                6243109
                30483231
                5b0ee5fc-1e04-4984-9b86-d816f5a47368
                Copyright © 2018 Bi, Kong, Qian, Jiang, Kang, Gu and Ma.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 June 2018
                : 23 October 2018
                Page count
                Figures: 4, Tables: 3, Equations: 1, References: 52, Pages: 11, Words: 7027
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                carbapenem,escherichia coli,blandm variants,diversity,plasmid
                Microbiology & Virology
                carbapenem, escherichia coli, blandm variants, diversity, plasmid

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