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Significance Bacterial adaptation to the presence of an antibiotic often involves evolutionary trade-offs, such as increased susceptibility to other drugs (collateral sensitivity). Its exploitation to design improved therapeutic strategies is… Click to show full abstract
Significance Bacterial adaptation to the presence of an antibiotic often involves evolutionary trade-offs, such as increased susceptibility to other drugs (collateral sensitivity). Its exploitation to design improved therapeutic strategies is only feasible if collateral sensitivity is robust, reproducible, and emerges in resistant mutants; these issues are rarely addressed in available publications. We describe a robust collateral sensitivity phenotype that emerges in different antibiotic-resistance mutational backgrounds, due to different genetic events, and propose therapeutic strategies effective for treating infections caused by Pseudomonas aeruginosa antibiotic-resistant mutants. Since conserved collateral sensitivity phenotypes do not confer adaptation to the presence of antibiotics, our results are also relevant for understanding convergent evolution processes in which the force selecting the emerging phenotype remains unclear.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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