1. Evolutionary Biology
  2. Microbiology and Infectious Disease
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Collateral sensitivity associated with antibiotic resistance plasmids

  1. Cristina Herencias
  2. Jerónimo Rodríguez-Beltrán  Is a corresponding author
  3. Ricardo León-Sampedro
  4. Aida Alonso-del Valle
  5. Jana Palkovičová
  6. Rafael Cantón
  7. Álvaro San Millán  Is a corresponding author
  1. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Spain
  2. Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences, Czech Republic
  3. Centro Nacional de Biotecnología-CSIC, Spain
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Cite this article as: eLife 2021;10:e65130 doi: 10.7554/eLife.65130

Abstract

Collateral sensitivity (CS) is a promising alternative approach to counteract the rising problem of antibiotic resistance (ABR). CS occurs when the acquisition of resistance to one antibiotic produces increased susceptibility to a second antibiotic. Recent studies have focused on CS strategies designed against ABR mediated by chromosomal mutations. However, one of the main drivers of ABR in clinically relevant bacteria is the horizontal transfer of ABR genes mediated by plasmids. Here, we report the first analysis of CS associated with the acquisition of complete ABR plasmids, including the clinically important carbapenem-resistance conjugative plasmid pOXA-48. In addition, we describe the conservation of CS in clinical E. coli isolates and its application to selectively kill plasmid-carrying bacteria. Our results provide new insights that establish the basis for developing CS-informed treatment strategies to combat plasmid-mediated ABR.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3 and S2.Sequencing data have been deposited in the Sequence Read Archive (SRA) repository, BioProject ID: PRJNA644278 (https://www.ncbi.nlm.nih.gov/bioproject/644278).

The following data sets were generated

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Author details

  1. Cristina Herencias

    Microbiology, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Jerónimo Rodríguez-Beltrán

    Microbiology, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
    For correspondence
    jeronimo.rodriguez.beltran@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3014-1229
  3. Ricardo León-Sampedro

    Microbiology, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5317-8310
  4. Aida Alonso-del Valle

    Microbiology, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Jana Palkovičová

    Department of Biology and Wildlife Diseases, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  6. Rafael Cantón

    Microbiology, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Álvaro San Millán

    Microbial Biotechnology, Centro Nacional de Biotecnología-CSIC, Madrid, Spain
    For correspondence
    asanmillan@cnb.csic.es
    Competing interests
    The authors declare that no competing interests exist.

Funding

European Research Council (ERC-StG 757440-PLASREVOLUTION)

  • Álvaro San Millán

Instituto de Salud Carlos III (PI16-00860)

  • Álvaro San Millán

Agencia Estatal de Investigación (IJC2018-035146-I)

  • Jerónimo Rodríguez-Beltrán

Instituto de Salud Carlos III (MS15-00012)

  • Álvaro San Millán

Comunidad Autonoma de Madrid (PEJD-2018-POST/BMD-8016)

  • Cristina Herencias

European Commission (R-GNOSIS-FP7-HEALTH-F3-2011-282512)

  • Rafael Cantón

Instituto de Salud Carlos III (REIPIR D16/0016/0011)

  • Rafael Cantón

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Marc Lipsitch, Harvard TH Chan School of Public Health, United States

Publication history

  1. Received: November 24, 2020
  2. Accepted: January 20, 2021
  3. Accepted Manuscript published: January 20, 2021 (version 1)
  4. Version of Record published: January 26, 2021 (version 2)

Copyright

© 2021, Herencias et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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