Integron activity accelerates the evolution of antibiotic resistance
- University of Oxford, United Kingdom
- 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.
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Adaptive benefits of integron shufflingEuropean Nucleotide Archive, PRJEB40301.
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Integron array MICs and cassettes transcription dataDryad Digital Repository, doi:10.5061/dryad.rv15dv469.
Article and author information
Author details
José Antonio Escudero
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.
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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Integron activity accelerates the evolution of antibiotic resistance
eLife 10:e62474.
https://doi.org/10.7554/eLife.62474
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