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Global transmission of extended-spectrum cephalosporin resistance in Escherichia coli driven by epidemic plasmids.
Zamudio, Roxana; Boerlin, Patrick; Mulvey, Michael R; Haenni, Marisa; Beyrouthy, Racha; Madec, Jean-Yves; Schwarz, Stefan; Cormier, Ashley; Chalmers, Gabhan; Bonnet, Richard; Zhanel, George G; Kaspar, Heike; Mather, Alison E.
Afiliação
  • Zamudio R; Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, United Kingdom.
  • Boerlin P; Department of Pathobiology, University of Guelph, Guelph N1G 2W1, Canada.
  • Mulvey MR; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
  • Haenni M; Unité Antibiorésistance et Virulence Bactériennes, Anses - Université de Lyon, Lyon 69007, France.
  • Beyrouthy R; Microbes Intestin Inflammation et Susceptibilité de l'Hôte (M2ISH), Faculté de Médecine, Université Clermont Auvergne, Clermont-Ferrand 63001, France; Centre National de Référence de la Résistance Aux Antibiotiques, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand 63000, France
  • Madec JY; Unité Antibiorésistance et Virulence Bactériennes, Anses - Université de Lyon, Lyon 69007, France.
  • Schwarz S; Institute of Microbiology and Epizootics, School of Veterinary Medicine, Freie Universität Berlin, Berlin 14163, Germany; Veterinary Centre for Resistance Research (TZR), School of Veterinary Medicine, Freie Universität Berlin, Berlin 14163, Germany.
  • Cormier A; Department of Pathobiology, University of Guelph, Guelph N1G 2W1, Canada.
  • Chalmers G; Department of Pathobiology, University of Guelph, Guelph N1G 2W1, Canada.
  • Bonnet R; Microbes Intestin Inflammation et Susceptibilité de l'Hôte (M2ISH), Faculté de Médecine, Université Clermont Auvergne, Clermont-Ferrand 63001, France; Centre National de Référence de la Résistance Aux Antibiotiques, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand 63000, France
  • Zhanel GG; Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
  • Kaspar H; Department Method Standardisation, Resistance to Antibiotics Unit Monitoring of Resistance to Antibiotics, Federal Office of Consumer Protection and Food Safety, Berlin 12277, Germany.
  • Mather AE; Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, United Kingdom; University of East Anglia, Norwich NR4 7TJ, United Kingdom. Electronic address: alison.mather@quadram.ac.uk.
EBioMedicine ; 103: 105097, 2024 May.
Article em En | MEDLINE | ID: mdl-38608515
ABSTRACT

BACKGROUND:

Extended-spectrum cephalosporins (ESCs) are third and fourth generation cephalosporin antimicrobials used in humans and animals to treat infections due to multidrug-resistant (MDR) bacteria. Resistance to ESCs (ESC-R) in Enterobacterales is predominantly due to the production of extended-spectrum ß-lactamases (ESBLs) and plasmid-mediated AmpC ß-lactamases (AmpCs). The dynamics of ESBLs and AmpCs are changing across countries and host species, the result of global transmission of ESC-R genes. Plasmids are known to play a key role in this dissemination, but the relative importance of different types of plasmids is not fully understood.

METHODS:

In this study, Escherichia coli with the major ESC-R genes blaCTX-M-1, blaCTX-M-15, blaCTX-M-14 (ESBLs) and blaCMY-2 (AmpC), were selected from diverse host species and other sources across Canada, France and Germany, collected between 2003 and 2017. To examine in detail the vehicles of transmission of the ESC-R genes, long- and short-read sequences were generated to obtain complete contiguous chromosome and plasmid sequences (n = 192 ESC-R E. coli). The types, gene composition and genetic relatedness of these plasmids were investigated, along with association with isolate year, source and geographical origin, and put in context with publicly available plasmid sequences.

FINDINGS:

We identified five epidemic resistance plasmid subtypes with distinct genetic properties that are associated with the global dissemination of ESC-R genes across multiple E. coli lineages and host species. The IncI1 pST3 blaCTX-M-1 plasmid subtype was found in more diverse sources than the other main plasmid subtypes, whereas IncI1 pST12 blaCMY-2 was more frequent in Canadian and German human and chicken isolates. Clonal expansion also contributed to the dissemination of the IncI1 pST12 blaCMY-2 plasmid in ST131 and ST117 E. coli harbouring this plasmid. The IncI1 pST2 blaCMY-2 subtype was predominant in isolates from humans in France, while the IncF F31A4B1 blaCTX-M-15 and F2A-B- blaCTX-M-14 plasmid subtypes were frequent in human and cattle isolates across multiple countries. Beyond their epidemic nature with respect to ESC-R genes, in our collection almost all IncI1 pST3 blaCTX-M-1 and IncF F31A4B1 blaCTX-M-15 epidemic plasmids also carried multiple antimicrobial resistance (AMR) genes conferring resistance to other antimicrobial classes. Finally, we found genetic signatures in the regions surrounding specific ESC-R genes, identifying the predominant mechanisms of ESC-R gene movement, and using publicly available databases, we identified these epidemic plasmids from widespread bacterial species, host species, countries and continents.

INTERPRETATION:

We provide evidence that epidemic resistance plasmid subtypes contribute to the global dissemination of ESC-R genes, and in addition, some of these epidemic plasmids confer resistance to multiple other antimicrobial classes. The success of these plasmids suggests that they may have a fitness advantage over other plasmid types and subtypes. Identification and understanding of the vehicles of AMR transmission are crucial to develop and target strategies and interventions to reduce the spread of AMR.

FUNDING:

This project was supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), through the Medical Research Council (MRC, MR/R000948/1), the Canadian Institutes of Health Research (CFC-150770), and the Genomics Research and Development Initiative (Government of Canada), the German Federal Ministry of Education and Research (BMBF) grant no. 01KI1709, the French Agency for food environmental and occupational health & safety (Anses), and the French National Reference Center (CNR) for antimicrobial resistance. Support was also provided by the Biotechnology and Biological Sciences Research Council (BBSRC) through the BBSRC Institute Strategic Programme Microbes in the Food ChainBB/R012504/1 and its constituent project BBS/E/F/000PR10348 (Theme 1, Epidemiology and Evolution of Pathogens in the Food Chain).
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plasmídeos / Resistência às Cefalosporinas / Escherichia coli / Infecções por Escherichia coli País/Região como assunto: Europa Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Reino Unido

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plasmídeos / Resistência às Cefalosporinas / Escherichia coli / Infecções por Escherichia coli País/Região como assunto: Europa Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Reino Unido