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 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.
Highlights
Given the mounting threat posed by antibiotic resistance, we need a better understanding of the mechanisms used by bacteria to evolve resistance to antibiotics
Mobile integrons are widespread genetic platforms involved in the interchange and expression of antibiotic resistance cassettes in bacteria
We tested this hypothesis by quantifying the impact of integrase activity on adaptation to increasing doses of gentamicin in populations of P. aeruginosa carrying a customized integron on a broad host range plasmid
Summary
Given the mounting threat posed by antibiotic resistance, we need a better understanding of the mechanisms used by bacteria to evolve resistance to antibiotics. Mobile integrons (MIs) are widespread elements providing a platform for the acquisition, shuffling, and expression of gene cassettes, many of which are antibiotic resistance genes (Recchia and Hall, 1995; Escudero et al, 2015). These elements are typically associated with transposons and conjugative plasmids and have played an important role in the evolution of resistance in pathogenic bacteria (Partridge et al, 2018).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
