1. Evolutionary Biology
  2. Microbiology and Infectious Disease
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Evolutionary stability of collateral sensitivity to antibiotics in the model pathogen Pseudomonas aeruginosa

Research Article
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Cite this article as: eLife 2019;8:e51481 doi: 10.7554/eLife.51481

Abstract

Evolution is at the core of the impending antibiotic crisis. Sustainable therapy must thus account for the adaptive potential of pathogens. One option is to exploit evolutionary trade-offs, like collateral sensitivity, where evolved resistance to one antibiotic causes hypersensitivity to another one. To date, the evolutionary stability and thus clinical utility of this trade-off is unclear. We performed a critical experimental test on this key requirement, using evolution experiments with Pseudomonas aeruginosa, and identified three main outcomes: (i) bacteria commonly failed to counter hypersensitivity and went extinct; (ii) hypersensitivity sometimes converted into multidrug resistance; and (iii) resistance gains frequently caused re-sensitization to the previous drug, thereby maintaining the trade-off. Drug order affected the evolutionary outcome, most likely due to variation in the effect size of collateral sensitivity, epistasis among adaptive mutations, and fitness costs. Our finding of robust genetic trade-offs and drug-order effects can guide design of evolution-informed antibiotic therapy.

Article and author information

Author details

  1. Camilo Barbosa

    Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Roderich Römhild

    Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Philip Rosenstiel

    Institute of Clinical Molecular Biology, University of Kiel, Kiel, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9692-8828
  4. Hinrich Schulenburg

    Department of Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany
    For correspondence
    hschulenburg@zoologie.uni-kiel.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1413-913X

Funding

Deutsche Forschungsgemeinschaft (SCHU 1415/12-1)

  • Hinrich Schulenburg

Deutsche Forschungsgemeinschaft (EXC 22167-39088401)

  • Philip Rosenstiel
  • Hinrich Schulenburg

Leibniz-Gemeinschaft (EvoLUNG)

  • Camilo Barbosa
  • Hinrich Schulenburg

Max-Planck-Gesellschaft (IMPRS Evolutionary Biology)

  • Camilo Barbosa
  • Roderich Römhild

Max-Planck-Gesellschaft (Fellowship)

  • Hinrich Schulenburg

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

Reviewing Editor

  1. Csaba Pal, Biological Research Centre of the Hungarian Academy of Sciences, Hungary

Publication history

  1. Received: August 30, 2019
  2. Accepted: October 21, 2019
  3. Accepted Manuscript published: October 29, 2019 (version 1)
  4. Version of Record published: November 27, 2019 (version 2)

Copyright

© 2019, Barbosa 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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