Integron activity accelerates the evolution of antibiotic resistance

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. Our results show that integrons accelerate resistance evolution by rapidly generating combinatorial variation in cassette composition while maintaining genomic integrity, and they highlight the importance of semi-conservative cassette excision for integron dynamics.

Threats of antibiotic resistance: an obliged reappraisal

“…In fact, the release in the environment of antibiotics, among other anthropogenic contaminants, increases the local density of harmful antibiotic resistance genes and also mobile genetic elements (Knapp et al 2010;Wright et al 2008;Gillings 2014). Increased density of mobile genetic elements implies an acceleration of the bacterial evolutionary rate (Souque et al 2021). In other words, antibiotic resistance might significantly increase the density of tools involved in microbial genetic interactions, once more with unpredictable consequences in shaping bacterial evolutionary trajectories that might influence human and animal health (Baquero et al 2021a(Baquero et al , 2021b.…”

Bacterial evolution on demand

“…Now, in eLife, Célia Souque, José A. Escudero and Craig MacLean of the University of Oxford and the Universidade Complutense de Madrid report new insights into how bacteria evolve on demand when exposed to antibiotic treatment ( Souque et al, 2021 ). Souque et al used two strains of the bacterium Pseudomonas aeruginosa , differing only by the presence or absence of a functional integrase.…”