1. Evolutionary Biology
Download icon

Rapid decline of bacterial drug-resistance in an antibiotic-free environment through phenotypic reversion

  1. Anett Dunai
  2. Reka Spohn
  3. Zoltán Farkas
  4. Viktoria Lazar
  5. Adam Gyorkei
  6. Gabor Apjok
  7. Gabor Boross
  8. Balazs Szappanos
  9. Gabor Grezal
  10. Aniko Farago
  11. Laszlo Bodai
  12. Balazs Papp
  13. Csaba Pal  Is a corresponding author
  1. Biological Research Centre of the Hungarian Academy of Sciences, Hungary
  2. University of Szeged, Hungary
Research Article
  • Cited 0
  • Views 1,603
  • Annotations
Cite this article as: eLife 2019;8:e47088 doi: 10.7554/eLife.47088

Abstract

Antibiotic resistance typically induces a fitness cost that shapes the fate of antibiotic-resistant bacterial populations. However, the cost of resistance can be mitigated by compensatory mutations elsewhere in the genome, and therefore the loss of resistance may proceed too slowly to be of practical importance. We present our study on the efficacy and phenotypic impact of compensatory evolution in Escherichia coli strains carrying multiple resistance mutations. We have demonstrated that drug-resistance frequently declines within 480 generations during exposure to an antibiotic-free environment. The extent of resistance loss was found to be generally antibiotic-specific, driven by mutations that reduce both resistance level and fitness costs of antibiotic-resistance mutations. We conclude that phenotypic reversion to the antibiotic-sensitive state can be mediated by the acquisition of additional mutations, while maintaining the original resistance mutations. Our study indicates that restricting antimicrobial usage could be a useful policy, but for certain antibiotics only.

Article and author information

Author details

  1. Anett Dunai

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  2. Reka Spohn

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  3. Zoltán Farkas

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5085-3306
  4. Viktoria Lazar

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  5. Adam Gyorkei

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  6. Gabor Apjok

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  7. Gabor Boross

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7208-5678
  8. Balazs Szappanos

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  9. Gabor Grezal

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  10. Aniko Farago

    Faculty of Science and Informatics, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  11. Laszlo Bodai

    Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8411-626X
  12. Balazs Papp

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  13. Csaba Pal

    Synthetic and Systems Biology Unit, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary
    For correspondence
    cpal@brc.hu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5187-9903

Funding

H2020 European Research Council (H2020-ERC-2014-CoG 648364 - Resistance Evolution)

  • Csaba Pal

Magyar Tudományos Akadémia (Lendület Programme LP 2012-32/2018)

  • Csaba Pal

Magyar Tudományos Akadémia (Postdoctoral Programme PD-007/2016)

  • Viktoria Lazar

Magyar Tudományos Akadémia (Postdoctoral Programme PD-038/2015)

  • Zoltán Farkas

National Research, Development and Innovation Office (NKFI-112294)

  • Laszlo Bodai

Magyar Tudományos Akadémia (Lendület Programme LP2009-013/2012)

  • Balazs Papp

Gazdaságfejlesztési és Innovációs Operatív Programm (GINOP-2.3.2-15-2016-00014)

  • Csaba Pal

Gazdaságfejlesztési és Innovációs Operatív Programm (GINOP-2.3.2-15-2016-00020)

  • Csaba Pal

Momentum Programme of the Hungarian Academy of Sciences (LP-2017-10/2017)

  • Csaba Pal

National Research, Development and Innovation Office (Élvonal Programme KKP 126506)

  • Csaba Pal

Wellcome Trust (WT 098016/Z/11/Z)

  • Balazs Papp

Gazdaságfejlesztési és Innovációs Operatív Programm (GINOP-2.3.2-15-2016-00026)

  • Balazs Papp

Wellcome Trust (WT 084314/Z/07/Z)

  • Csaba Pal

National Research, Development and Innovation Office (FK 128775)

  • Zoltán Farkas

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

Reviewing Editor

  1. Christian R Landry, Université Laval, Canada

Publication history

  1. Received: March 22, 2019
  2. Accepted: August 5, 2019
  3. Accepted Manuscript published: August 16, 2019 (version 1)
  4. Version of Record published: August 23, 2019 (version 2)

Copyright

© 2019, Dunai 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.

Metrics

  • 1,603
    Page views
  • 246
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Evolutionary Biology
    Adérito L Monjane et al.
    Research Article
    1. Evolutionary Biology
    Kristina Crona
    Research Advance