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      Structure, Genetics and Worldwide Spread of New Delhi Metallo-β-lactamase (NDM): a threat to public health

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          Abstract

          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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          Most cited references109

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          Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

          Summary Background Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK. Methods Enterobacteriaceae isolates were studied from two major centres in India—Chennai (south India), Haryana (north India)—and those referred to the UK's national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene bla NDM-1 was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan. Findings We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries. Interpretation The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed. Funding European Union, Wellcome Trust, and Wyeth.
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            Carbapenemases: the versatile beta-lactamases.

            Carbapenemases are beta-lactamases with versatile hydrolytic capacities. They have the ability to hydrolyze penicillins, cephalosporins, monobactams, and carbapenems. Bacteria producing these beta-lactamases may cause serious infections in which the carbapenemase activity renders many beta-lactams ineffective. Carbapenemases are members of the molecular class A, B, and D beta-lactamases. Class A and D enzymes have a serine-based hydrolytic mechanism, while class B enzymes are metallo-beta-lactamases that contain zinc in the active site. The class A carbapenemase group includes members of the SME, IMI, NMC, GES, and KPC families. Of these, the KPC carbapenemases are the most prevalent, found mostly on plasmids in Klebsiella pneumoniae. The class D carbapenemases consist of OXA-type beta-lactamases frequently detected in Acinetobacter baumannii. The metallo-beta-lactamases belong to the IMP, VIM, SPM, GIM, and SIM families and have been detected primarily in Pseudomonas aeruginosa; however, there are increasing numbers of reports worldwide of this group of beta-lactamases in the Enterobacteriaceae. This review updates the characteristics, epidemiology, and detection of the carbapenemases found in pathogenic bacteria.
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              Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America.

              The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, "Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews," and recently issued a "Call to Action" to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure--one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.
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                Author and article information

                Contributors
                00919837021912 , asad.k@rediffmail.com
                lucymary20@gmail.com
                00390817463026 , rafzarri@unina.it
                Journal
                BMC Microbiol
                BMC Microbiol
                BMC Microbiology
                BioMed Central (London )
                1471-2180
                27 April 2017
                27 April 2017
                2017
                : 17
                : 101
                Affiliations
                [1 ]ISNI 0000 0004 1937 0765, GRID grid.411340.3, Medical Microbiology and Molecular Biology Laboratory, Interdisciplinary Biotechnology Unit, , Aligarh Muslim University, ; Aligarh, 202002 India
                [2 ]ISNI 0000 0001 0790 385X, GRID grid.4691.a, Department of Public Health, , University of Napoli Federico II, ; Italy, Naples, Italy
                [3 ]ISNI 0000 0001 0790 385X, GRID grid.4691.a, , CEINGE Biotecnologie Avanzate, ; Naples, Italy
                Author information
                http://orcid.org/0000-0003-4191-9032
                Article
                1012
                10.1186/s12866-017-1012-8
                5408368
                28449650
                bde596f3-84f6-4e45-b786-fb67a5f6d805
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 15 March 2017
                : 14 April 2017
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Microbiology & Virology
                enterobacteriaceae,new delhi-metallo-beta-lactamases,carbapenemases,antibiotic resistance

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