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• W4238984986 abstract "In response to the Yi-Yun Liu and colleagues' finding of a mobile genetic element responsible for colistin resistance, mcr-1,1Liu Y-Y Wang Y Walsh TR et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.Lancet Infect Dis. 2015; (published online Nov 18.)http://dx.doi.org/10.1016/S1473-3099(15)00424-7Google Scholar and the accompanying Comment asking “is plasmid-mediated colistin resistance a purely Chinese phenomenon?”2Paterson DL Harris PN Colistin resistance: a major breach in our last line of defence.Lancet Infect Dis. 2015; (published online Nov 18.)http://dx.doi.org/10.1016/S1473-3099(15)00463-6Google Scholar, we, and others,3Hasman H Hammerum A Hansen F et al.Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015.Eurosurveillance. 2015; (published online Dec 10.)http://dx.doi.org/10.2807/1560-7917.ES.2015.20.49.30085Google Scholar, 4Public Health England (PHE)First detection of plasmid-mediated colistin resistance (mcr-1 gene) in food and human isolates in England and Wales (Serial number 2015/090). Public Health England, London2015Google Scholar can now reply no. As part of routine surveillance, we screened 8684 salmonella isolates collected during 2012–13 from the French agricultural food sector for colistin resistance using disk diffusion.5Clinical and Laboratory Standards InstituteCLSI document M02-A11: performance standards for antimicrobial disk susceptibility tests; approved standard. 11th edn. Clinical and Laboratory Standards Institute, Wayne2012Google Scholar Between October and December, 2013, 27 isolates that showed a reduced susceptibility to colistin (ie, zone of inhibition <15 mm) were further assessed using a colistin concentration gradient assay. Five isolates (0·06%) had a distinctly different minimum inhibitory concentration (≥4 mg/mL) and were defined as colistin-resistant. In 2014, whole-genome sequencing of the five isolates was done and resultant sequences were assembled and interrogated for mutations and genetic elements associated with colistin resistance. We identified mcr-1 in four of five phenotypically colistin-resistant isolates. Furthermore, mcr-1 was associated with plasmid DNA and in silico replicon typing identified various plasmid backbones that were distinct from those reported by Liu and colleagues (table).1Liu Y-Y Wang Y Walsh TR et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.Lancet Infect Dis. 2015; (published online Nov 18.)http://dx.doi.org/10.1016/S1473-3099(15)00424-7Google Scholar The isolates harboured a 1626 bp sequence with 100% homology to the recently described mcr-1.1Liu Y-Y Wang Y Walsh TR et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.Lancet Infect Dis. 2015; (published online Nov 18.)http://dx.doi.org/10.1016/S1473-3099(15)00424-7Google Scholar Colistin resistance, although extraordinarily rare, was reported in epidemiologically, regionally, and serologically unrelated salmonella isolates, and, surprisingly, all were of the O:4 serogroup (serotypes Derby, Schwarzengrund, 1,4,[5],12:i:-, and Paratyphi B). Whether the product of mcr-1, MCR-1, confers resistance in a limited number of lipopolysaccharide structures or whether our findings were a remarkable coincidence is unclear. If not coincidental, this finding might offer the prospect of limited dissemination within the salmonella genus and this potentially warrants further investigation in Enterobacteriaceae. Interrogation of the genomes using nucleotide alignment of genes previously associated with colistin resistance in Enterobacteriaceae, specifically pmrAB, phoPQ, and mgrB,6Olaitan AO Morand S Rolain JM Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria.Front Microbiol. 2014; 5: 18Crossref PubMed Scopus (821) Google Scholar showed no mutations that explained the resistant phenotype. The genomes of the four mcr-1-positive strains were deposited in GenBank under the accession numbers LNCZ00000000, LKJK00000000, LKJJ00000000, and LKJD00000000.TableIsolate information for mcr-1 positive isolates selected for whole genome sequencing2013LSAL0237412CEB4337SAL12CEB2196SAL2013LSAL04524SerotypeDerbyParatyphi BParatyphi B1,4,[5],12:i:-Year2013201220122013Sample typeChipolata sausageReady-to-cook guinea fowl pieChicken breast with skinBoot swabs from broiler farmFrench department62568501AMPNon-resNon-resNon-resResAMCNon-resNon-resNon-resNon-resCAZNon-resNon-resNon-resNon-resCHLResResResResCEFNon-resNon-resNon-resNon-resCIPNon-resResResNon-resCSTResResResResCTXNon-resNon-resNon-resNon-resGENNon-resResResResKANNon-resNon-resNon-resNon-resNALNon-resResResNon-resOFXNon-resNon-resNon-resNon-resSTRResResResResSSSResResResResSXTResResResResTETResResResResGenBank accession numberLNCZ00000000LKJK00000000LKJJ00000000LKJD00000000Plasmid replicon harbouring mcr-1IncPIncX4IncX4IncPAMP=ampicillin. AMC=amoxicillin-clavulanic acid. CAZ=ceftazidime. CHL=chloramphenicol. CEF=cephalotin. CIP=ciprofloxacin. CST=colistin. CTX=cefotaxime. GEN=gentamicin. KAN=kanamycin. NAL=nalidixic acid. OFX=ofloxacine. STR=streptomycin. SSS=sulfonamides. SXT=trimethoprim-sulfamethoxazole (co-trimoxazole). TET=tetracycline. Res=resistance. Non-res=not resistant. Open table in a new tab AMP=ampicillin. AMC=amoxicillin-clavulanic acid. CAZ=ceftazidime. CHL=chloramphenicol. CEF=cephalotin. CIP=ciprofloxacin. CST=colistin. CTX=cefotaxime. GEN=gentamicin. KAN=kanamycin. NAL=nalidixic acid. OFX=ofloxacine. STR=streptomycin. SSS=sulfonamides. SXT=trimethoprim-sulfamethoxazole (co-trimoxazole). TET=tetracycline. Res=resistance. Non-res=not resistant. Broader distribution—in terms of geography and bacterial genera—of plasmid-associated mcr-1 is evident because it has now been identified outside Asia.1Liu Y-Y Wang Y Walsh TR et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.Lancet Infect Dis. 2015; (published online Nov 18.)http://dx.doi.org/10.1016/S1473-3099(15)00424-7Google Scholar Saliently, we describe its presence in an important foodborne pathogen recovered from food and animal environments and associated with well described phenotypic resistance (by disk diffusion, broth microdilution, and concentration gradient strips). Furthermore, mcr-1 has now been associated with several plasmid incompatibility types. If these plasmids do contain the mcr-1 gene, as suggested by our interrogation of the draft genomes, and are mobile, or at least mobilisable, dissemination of these plasmids harbouring mcr-1 in salmonella and other bacteria seems possible, if not probable. Interrogation of other horizontally transferable elements will provide broader understanding of the probable distribution of this gene. Our findings, and those of others,1Liu Y-Y Wang Y Walsh TR et al.Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.Lancet Infect Dis. 2015; (published online Nov 18.)http://dx.doi.org/10.1016/S1473-3099(15)00424-7Google Scholar reinforce the need to reconsider the use of in-feed colistin in veterinary medicine at a worldwide level. Stewardship efforts are needed to preserve the efficacy of antimicrobial drugs for society—both now and into the future. Effective strategies that limit selection and further dissemination of plasmid-associated mcr-1 are clearly needed. This work was supported by the Antimicrobial Resistance Unit, Laboratory for Food Safety, ANSES; United States Department of Agriculture (USDA), National Institutes of Food and Agriculture, National Integrated Food Safety Initiative award number 2010-51110-21083; and the USDA Agricultural Research Service project number 0204-41510-001-47G. Support for HEW was provided by the Embassy of France in the US Chateaubriand Fellowship program and by a graduate student assistantship from the Houston Livestock Show and Rodeo. GHL and HMS have provided scientific advice to various pharmaceutical companies that market antimicrobial drugs for administration to animals. They have, on occasion, billed for their service. They have also received honoraria and travel support for service on advisory boards and presentations from pharmaceutical companies. All other authors declare no competing interests. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological studyThe emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Full-Text PDF" @default.
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• W4238984986 title "Dissemination of the mcr-1 colistin resistance gene" @default.
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