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      Heavy Metal Resistance Genes Are Associated with bla NDM-1- and bla CTX-M-15-Carrying Enterobacteriaceae

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          ABSTRACT

          The occurrence of heavy metal resistance genes in multiresistant Enterobacteriaceae possessing bla NDM-1 or bla CTX-M-15 genes was examined by PCR and pulsed-field gel electrophoresis with S1 nuclease. Compared with clinical susceptible isolates (10.0% to 30.0%), the pcoA, merA, silC, and arsA genes occurred with higher frequencies in bla NDM-1-positive (48.8% to 71.8%) and bla CTX-M-15-positive (19.4% to 52.8%) isolates, and they were mostly located on plasmids. Given the high association of metal resistance genes with multidrug-resistant Enterobacteriaceae, increased vigilance needs to be taken with the use of heavy metals in hospitals and the environment.

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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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            Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study.

            Not all patients infected with NDM-1-positive bacteria have a history of hospital admission in India, and extended-spectrum β-lactamases are known to be circulating in the Indian community. We therefore measured the prevalence of the NDM-1 gene in drinking water and seepage samples in New Delhi. Swabs absorbing about 100 μL of seepage water (ie, water pools in streets or rivulets) and 15 mL samples of public tap water were collected from sites within a 12 km radius of central New Delhi, with each site photographed and documented. Samples were transported to the UK and tested for the presence of the NDM-1 gene, bla(NDM-1), by PCR and DNA probing. As a control group, 100 μL sewage effluent samples were taken from the Cardiff Wastewater Treatment Works, Tremorfa, Wales. Bacteria from all samples were recovered and examined for bla(NDM-1) by PCR and sequencing. We identified NDM-1-positive isolates, undertook susceptibility testing, and, where appropriate, typed the isolates. We undertook Inc typing on bla(NDM-1)-positive plasmids. Transconjugants were created to assess plasmid transfer frequency and its relation to temperature. From Sept 26 to Oct 10, 2010, 171 seepage samples and 50 tap water samples from New Delhi and 70 sewage effluent samples from Cardiff Wastewater Treatment Works were collected. We detected bla(NDM-1) in two of 50 drinking-water samples and 51 of 171 seepage samples from New Delhi; the gene was not found in any sample from Cardiff. Bacteria with bla(NDM-1) were grown from 12 of 171 seepage samples and two of 50 water samples, and included 11 species in which NDM-1 has not previously been reported, including Shigella boydii and Vibrio cholerae. Carriage by enterobacteria, aeromonads, and V cholera was stable, generally transmissible, and associated with resistance patterns typical for NDM-1; carriage by non-fermenters was unstable in many cases and not associated with typical resistance. 20 strains of bacteria were found in the samples, 12 of which carried bla(NDM-1) on plasmids, which ranged in size from 140 to 400 kb. Isolates of Aeromonas caviae and V cholerae carried bla(NDM-1) on chromosomes. Conjugative transfer was more common at 30°C than at 25°C or 37°C. The presence of NDM-1 β-lactamase-producing bacteria in environmental samples in New Delhi has important implications for people living in the city who are reliant on public water and sanitation facilities. International surveillance of resistance, incorporating environmental sampling as well as examination of clinical isolates, needs to be established as a priority. European Union. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Intercontinental emergence of Escherichia coli clone O25:H4-ST131 producing CTX-M-15.

              Concomitant with the recent emergence of CTX-M-type extended-spectrum beta-lactamases (ESBLs), Escherichia coli has become the enterobacterial species most affected by ESBLs. Multiple locales are encountering CTX-M-positive E. coli, including specifically CTX-M-15. To gain insights into the mechanism underlying this phenomenon, we assessed clonality and diversity of virulence profiles within an international collection of CTX-M-15-positive E. coli. Forty-one ESBL-positive E. coli isolates from eight countries and three continents (Europe, Asia and North America) were selected for study based on suspected clonality. Phylogenetic group, ERIC2 PCR profile, O H serotype, AmpC variant and antibiotic susceptibility were determined. Multilocus sequence typing (MLST) and PFGE provided additional discrimination. Virulence potential was inferred by detection of 46 virulence factor (VF) genes. Thirty-six (88%) of the 41 E. coli isolates exhibited the same set of core characteristics: phylogenetic group B2, ERIC2 PCR profile 1, serotype O25:H4, AmpC EC6, ciprofloxacin resistance and MLST profile ST131. By PFGE, the 36 isolates constituted one large cluster at the 68% similarity level; this comprised 17 PFGE groups (defined at 85% similarity), some of which included strains from different countries. The 36 isolates exhibited highly (91% to 100%) similar VF profiles. We describe a broadly disseminated, CTX-M-15-positive and virulent E. coli clonal group with highly homogeneous virulence genotypes and subgroups exhibiting highly similar PFGE profiles, suggesting recent emergence. Understanding how this clone has emerged and successfully disseminated within the hospital and community, including across national boundaries, should be a public health priority.
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                Author and article information

                Journal
                Antimicrob Agents Chemother
                Antimicrob. Agents Chemother
                aac
                aac
                AAC
                Antimicrobial Agents and Chemotherapy
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                0066-4804
                1098-6596
                5 March 2018
                26 April 2018
                May 2018
                26 April 2018
                : 62
                : 5
                : e02642-17
                Affiliations
                [a ]Department of Medical Microbiology and Infectious Disease, Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom
                Author notes
                Address correspondence to Qiu E. Yang, yangqe@ 123456cardiff.ac.uk , or Timothy Rutland Walsh, walshtr@ 123456cardiff.ac.uk .

                Citation Yang QE, Agouri SR, Tyrrell JM, Walsh TR. 2018. Heavy metal resistance genes are associated with bla NDM-1- and bla CTX-M-15-carrying Enterobacteriaceae. Antimicrob Agents Chemother 62:e02642-17. https://doi.org/10.1128/AAC.02642-17.

                Article
                02642-17
                10.1128/AAC.02642-17
                5923091
                29507071
                b1312bdb-ec97-46dd-b816-a8bb11e84332
                Copyright © 2018 Yang et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 1 January 2018
                : 31 January 2018
                : 27 February 2018
                Page count
                supplementary-material: 1, Figures: 2, Tables: 2, Equations: 0, References: 20, Pages: 7, Words: 3547
                Categories
                Mechanisms of Resistance
                Custom metadata
                May 2018

                Infectious disease & Microbiology
                heavy metal resistance,blandm-1,blactx-m-15,plasmids,coresistance

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