Cargando…

Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages

Third-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 inc...

Descripción completa

Detalles Bibliográficos
Autores principales: de Been, Mark, Lanza, Val F., de Toro, María, Scharringa, Jelle, Dohmen, Wietske, Du, Yu, Hu, Juan, Lei, Ying, Li, Ning, Tooming-Klunderud, Ave, Heederik, Dick J. J., Fluit, Ad C., Bonten, Marc J. M., Willems, Rob J. L., de la Cruz, Fernando, van Schaik, Willem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270446/
https://www.ncbi.nlm.nih.gov/pubmed/25522320
http://dx.doi.org/10.1371/journal.pgen.1004776
_version_ 1782349499027423232
author de Been, Mark
Lanza, Val F.
de Toro, María
Scharringa, Jelle
Dohmen, Wietske
Du, Yu
Hu, Juan
Lei, Ying
Li, Ning
Tooming-Klunderud, Ave
Heederik, Dick J. J.
Fluit, Ad C.
Bonten, Marc J. M.
Willems, Rob J. L.
de la Cruz, Fernando
van Schaik, Willem
author_facet de Been, Mark
Lanza, Val F.
de Toro, María
Scharringa, Jelle
Dohmen, Wietske
Du, Yu
Hu, Juan
Lei, Ying
Li, Ning
Tooming-Klunderud, Ave
Heederik, Dick J. J.
Fluit, Ad C.
Bonten, Marc J. M.
Willems, Rob J. L.
de la Cruz, Fernando
van Schaik, Willem
author_sort de Been, Mark
collection PubMed
description Third-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.
format Online
Article
Text
id pubmed-4270446
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-42704462014-12-26 Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages de Been, Mark Lanza, Val F. de Toro, María Scharringa, Jelle Dohmen, Wietske Du, Yu Hu, Juan Lei, Ying Li, Ning Tooming-Klunderud, Ave Heederik, Dick J. J. Fluit, Ad C. Bonten, Marc J. M. Willems, Rob J. L. de la Cruz, Fernando van Schaik, Willem PLoS Genet Research Article Third-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. Public Library of Science 2014-12-18 /pmc/articles/PMC4270446/ /pubmed/25522320 http://dx.doi.org/10.1371/journal.pgen.1004776 Text en © 2014 de Been et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
de Been, Mark
Lanza, Val F.
de Toro, María
Scharringa, Jelle
Dohmen, Wietske
Du, Yu
Hu, Juan
Lei, Ying
Li, Ning
Tooming-Klunderud, Ave
Heederik, Dick J. J.
Fluit, Ad C.
Bonten, Marc J. M.
Willems, Rob J. L.
de la Cruz, Fernando
van Schaik, Willem
Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages
title Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages
title_full Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages
title_fullStr Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages
title_full_unstemmed Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages
title_short Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages
title_sort dissemination of cephalosporin resistance genes between escherichia coli strains from farm animals and humans by specific plasmid lineages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270446/
https://www.ncbi.nlm.nih.gov/pubmed/25522320
http://dx.doi.org/10.1371/journal.pgen.1004776
work_keys_str_mv AT debeenmark disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT lanzavalf disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT detoromaria disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT scharringajelle disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT dohmenwietske disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT duyu disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT hujuan disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT leiying disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT lining disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT toomingklunderudave disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT heederikdickjj disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT fluitadc disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT bontenmarcjm disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT willemsrobjl disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT delacruzfernando disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages
AT vanschaikwillem disseminationofcephalosporinresistancegenesbetweenescherichiacolistrainsfromfarmanimalsandhumansbyspecificplasmidlineages