Integron activity accelerates the evolution of antibiotic resistance

  1. Célia Souque  Is a corresponding author
  2. José Antonio Escudero
  3. R Craig MacLean
  1. University of Oxford, United Kingdom
  2. Institut Pasteur, France

Abstract

Mobile integrons are widespread genetic platforms that allow bacteria to modulate the expression of antibiotic resistance cassettes by shuffling their position from a common promoter. Antibiotic stress induces the expression of an integrase that excises and integrates cassettes, and this unique recombination and expression system is thought to allow bacteria to 'evolve on demand' in response to antibiotic pressure. To test this hypothesis, we inserted a custom three cassette integron into P. aeruginosa, and used experimental evolution to measure the impact of integrase activity on adaptation to gentamicin. Crucially, integrase activity accelerated evolution by increasing the expression of a gentamicin resistance cassette through duplications and by eliminating redundant cassettes. Importantly, we found no evidence of deleterious off-target effects of integrase activity. In summary, integrons accelerate resistance evolution by rapidly generating combinatorial variation in cassette composition while maintaining genomic integrity.

Data availability

Sequencing data have been deposited on ENA under the accession code PRJEB40301Source data files have been deposited on Dryad for Figures 1,2,3 and Figure 1 - Supplementary Figure 1.All other data generated or analysed during this study are included in the manuscript and supporting files.

The following data sets were generated

Article and author information

Author details

  1. Célia Souque

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    For correspondence
    celia.souque@zoo.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7194-4322
  2. José Antonio Escudero

    Genomes and Genetics, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8552-2956
  3. R Craig MacLean

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Funding

Wellcome Trust (106918/Z/15/Z)

  • R Craig MacLean

Biotechnology and Biological Sciences Research Council (BB/M011224/1)

  • Célia Souque

H2020 European Research Council (803375)

  • José Antonio Escudero

Comunidad de Madrid (2016-T1/BIO-1105)

  • José Antonio Escudero

Ministerio de Ciencia, Innovación y Universidades (BIO2017-85056-P)

  • José Antonio Escudero

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

Reviewing Editor

  1. Gisela Storz, National Institute of Child Health and Human Development, United States

Version history

  1. Received: August 25, 2020
  2. Accepted: February 23, 2021
  3. Accepted Manuscript published: February 26, 2021 (version 1)
  4. Version of Record published: April 6, 2021 (version 2)

Copyright

© 2021, Souque 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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  1. Célia Souque
  2. José Antonio Escudero
  3. R Craig MacLean
(2021)
Integron activity accelerates the evolution of antibiotic resistance
eLife 10:e62474.
https://doi.org/10.7554/eLife.62474

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