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      Novel plasmid-mediated colistin resistance mcr-4 gene in Salmonella and Escherichia coli, Italy 2013, Spain and Belgium, 2015 to 2016

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          Abstract

          A novel mcr colistin resistance gene was identified in a strain of Salmonella enterica, monophasic variant of serovar Typhimurium (4,5,12:i:- ), isolated from a pig at slaughter in Italy in 2013, and in Escherichia coli strains collected during routine diagnostic of post-weaning diarrhoea in pigs from Spain and Belgium in 2015 and 2016. Immediate implementation of mcr-screening including this novel gene variant is required for Salmonella and E. coli from humans and food-producing animals in Europe.

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          Novel Plasmid-Mediated Colistin Resistance Gene mcr-3 in Escherichia coli

          ABSTRACT The mobile colistin resistance gene mcr-1 has attracted global attention, as it heralds the breach of polymyxins, one of the last-resort antibiotics for the treatment of severe clinical infections caused by multidrug-resistant Gram-negative bacteria. To date, six slightly different variants of mcr-1, and a second mobile colistin resistance gene, mcr-2, have been reported or annotated in the GenBank database. Here, we characterized a third mobile colistin resistance gene, mcr-3. The gene coexisted with 18 additional resistance determinants in the 261-kb IncHI2-type plasmid pWJ1 from porcine Escherichia coli. mcr-3 showed 45.0% and 47.0% nucleotide sequence identity to mcr-1 and mcr-2, respectively, while the deduced amino acid sequence of MCR-3 showed 99.8 to 100% and 75.6 to 94.8% identity to phosphoethanolamine transferases found in other Enterobacteriaceae species and in 10 Aeromonas species, respectively. pWJ1 was mobilized to an E. coli recipient by conjugation and contained a plasmid backbone similar to those of other mcr-1-carrying plasmids, such as pHNSHP45-2 from the original mcr-1-harboring E. coli strain. Moreover, a truncated transposon element, TnAs2, which was characterized only in Aeromonas salmonicida, was located upstream of mcr-3 in pWJ1. This ΔTnAs2-mcr-3 element was also identified in a shotgun genome sequence of a porcine E. coli isolate from Malaysia, a human Klebsiella pneumoniae isolate from Thailand, and a human Salmonella enterica serovar Typhimurium isolate from the United States. These results suggest the likelihood of a wide dissemination of the novel mobile colistin resistance gene mcr-3 among Enterobacteriaceae and aeromonads; the latter may act as a potential reservoir for mcr-3.
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            Resistance to colistin: what is the fate for this antibiotic in pig production?

            Colistin, a cationic polypeptide antibiotic, has reappeared in human medicine as a last-line treatment option for multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin is widely used in veterinary medicine for the treatment of gastrointestinal infections caused by Enterobacteriaceae. GNB resistant to colistin owing to chromosomal mutations have already been reported both in human and veterinary medicine, however several recent studies have just identified a plasmid-mediated mcr-1 gene encoding for colistin resistance in Escherichia coli colistin resistance. The discovery of a non-chromosomal mechanism of colistin resistance in E. coli has led to strong reactions in the scientific community and to concern among physicians and veterinarians. Colistin use in food animals and particularly in pig production has been singled out as responsible for the emergence of colistin resistance. The present review will focus mainly on the possible link between colistin use in pigs and the spread of colistin resistance in Enterobacteriaceae. First we demonstrate a possible link between Enterobacteriaceae resistance emergence and oral colistin pharmacokinetics/pharmacodynamics and its administration modalities in pigs. We then discuss the potential impact of colistin use in pigs on public health with respect to resistance. We believe that colistin use in pig production should be re-evaluated and its dosing and usage optimised. Moreover, the search for competitive alternatives to using colistin with swine is of paramount importance to preserve the effectiveness of this antibiotic for the treatment of MDR-GNB infections in human medicine.
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              Association between pigs with high caecal Salmonella loads and carcass contamination.

              Contaminated pork is a significant source of foodborne Salmonella infections. Pork is contaminated at the slaughterhouse; however, the mechanisms driving Salmonella contamination of carcasses are still poorly understood. The aim of this study was to investigate whether the amount of Salmonella carried by slaughtered pigs in their guts has an influence on carcass contamination. On that account, we tested whether the number of carcasses contaminated during a slaughter day was associated with the prevalence of highly contaminated pigs (HCP: Salmonella caecal loads ≥3log/g), or with the prevalence of pigs that simply carry Salmonella spp. in their guts. Three hundred and six pigs were sampled in a slaughterhouse from Central Italy. Salmonella loads in the caecum and on the carcass of each pig were estimated by the most probable number (MPN) technique. The overall prevalence of Salmonella was 34.64% and 7.19% for the caeca and carcasses, respectively. S. Derby and Salmonella enterica 4,[5],12:i:- were the most frequently isolated serovars. The prevalence of HCP was 11.44%. We found a higher number of contaminated carcasses on days of high prevalence of HCP than on days of low prevalence of HCP (p=0.0011). Conversely, carcass contamination did not vary with the prevalence of pigs that simply carried Salmonella spp. in their guts (p=0.7970). Therefore, the prevalence of HCP, but not the prevalence of pigs carrying Salmonella spp., was related to carcass contamination. Taken together, these findings suggest that reduction of Salmonella loads in the guts of slaughtered pigs would result in fewer contaminated carcasses, and consequently, help to minimise the risk of human infection due to the consumption of contaminated pork.
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                Author and article information

                Journal
                Euro Surveill
                Euro Surveill
                ES
                Eurosurveillance
                European Centre for Disease Prevention and Control (ECDC)
                1025-496X
                1560-7917
                03 August 2017
                : 22
                : 31
                : 30589
                Affiliations
                [1 ]Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
                [2 ]Institute of Microbiology and Epizootics, Centre for Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany
                [3 ]Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche, Perugia, Italy
                [4 ]Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna, Reggio Emilia, Italy
                Author notes

                Correspondence: Alessandra Carattoli ( alessandra.carattoli@ 123456iss.it )

                Article
                17-00522 30589
                10.2807/1560-7917.ES.2017.22.31.30589
                5553062
                28797329
                ed6bcf09-537c-4565-b839-43bc8b711ac9
                This article is copyright of The Authors, 2017.

                This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0) Licence. You may share and adapt the material, but must give appropriate credit to the source, provide a link to the licence, and indicate if changes were made.

                History
                : 27 July 2017
                : 03 August 2017
                Categories
                Rapid Communication

                colistin,cole,salmonella,mcr
                colistin, cole, salmonella, mcr

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