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dc.contributor.authorBeen, Mark de-
dc.contributor.authorLanza, Val F.-
dc.contributor.authorToro, María de-
dc.contributor.authorCruz, Fernando de la-
dc.identifierdoi: 10.1371/journal.pgen.1004776-
dc.identifiere-issn: 1553-7404-
dc.identifierissn: 1553-7390-
dc.identifier.citationPLoS Genetics 10(12): e1004776 (2014)-
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.-
dc.description.abstractThird-generation cephalosporins are a class of β-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria, especially Escherichia coli. Worryingly, the incidence of human infections caused by third-generation cephalosporin-resistant E. coli is increasing worldwide. Recent studies have suggested that these E. coli strains, and their antibiotic resistance genes, can spread from food-producing animals, via the food-chain, to humans. However, these studies used traditional typing methods, which may not have provided sufficient resolution to reliably assess the relatedness of these strains. We therefore used whole-genome sequencing (WGS) to study the relatedness of cephalosporin-resistant E. coli from humans, chicken meat, poultry and pigs. One strain collection included pairs of human and poultry-associated strains that had previously been considered to be identical based on Multi-Locus Sequence Typing, plasmid typing and antibiotic resistance gene sequencing. The second collection included isolates from farmers and their pigs. WGS analysis revealed considerable heterogeneity between human and poultry-associated isolates. The most closely related pairs of strains from both sources carried 1263 Single-Nucleotide Polymorphisms (SNPs) per Mbp core genome. In contrast, epidemiologically linked strains from humans and pigs differed by only 1.8 SNPs per Mbp core genome. WGS-based plasmid reconstructions revealed three distinct plasmid lineages (IncI1- and IncK-type) that carried cephalosporin resistance genes of the Extended-Spectrum Beta-Lactamase (ESBL)- and AmpC-types. The plasmid backbones within each lineage were virtually identical and were shared by genetically unrelated human and animal isolates. Plasmid reconstructions from short-read sequencing data were validated by long-read DNA sequencing for two strains. Our findings failed to demonstrate evidence for recent clonal transmission of cephalosporin-resistant E. coli strains from poultry to humans, as has been suggested based on traditional, low-resolution typing methods. Instead, our data suggest that cephalosporin resistance genes are mainly disseminated in animals and humans via distinct plasmids.-
dc.description.sponsorshipThis work was supported by The European Union Seventh Framework (http://ec.europa.eu/research/fp7/) Programmes ‘‘Evolution and Transfer of Antibiotic Resistance’’ (EvoTAR; FP7-HEALTH-2011-single-stage; grant number 282004; to MdB, VFL, MdT, RJLW, FdlC, and WvS), and ‘‘Plaswires’’ (FP7 ICT 2009 4; grant number 248919; to VFL, MdT, and FdlC), the Spanish Ministry of Education (http://www.mecd.gob.es/portada-mecd/) (BFU2011 26608; to VFL, MdT, and FdlC), and The Netherlands Organisation for Research and Development ZonMw (http://www.nwo.nl/) (Contract number 50-51700-98-053; to WD).-
dc.publisherPublic Library of Science-
dc.relation.isversionofPublisher's version-
dc.titleDissemination of cephalosporin resistance genes between Escherichia coli strains from farm animals and humans by specific plasmid lineages-
dc.description.versionPeer Reviewed-
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España)-
dc.contributor.funderNetherlands Organisation for Health Research and Development-
dc.contributor.funderEuropean Commission-
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