Journal
ELIFE
Volume 10, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.62474
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Funding
- Wellcome Trust [106918/Z/15/Z]
- Biotechnology and Biological Sciences Research Council [BB/M011224/1]
- H2020 European Research Council [803375]
- Comunidad de Madrid [2016-T1/BIO-1105]
- Ministerio de Ciencia, Innovacion y Universidades [BIO2017-85056-P]
- European Research Council (ERC) [803375] Funding Source: European Research Council (ERC)
- BBSRC [1810153] Funding Source: UKRI
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Integrons accelerate resistance evolution by rapidly generating combinatorial variation in cassette composition while maintaining genomic integrity.
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 Pseudomonas 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.
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