Rapid Phenotypic Convergence towards Collateral Sensitivity in Clinical Isolates of Pseudomonas aeruginosa Presenting Different Genomic Backgrounds
Sara Hernando‐Amado, Carla López-Causapé, Pablo Laborda, Fernando Sanz‐García, Antonio Oliver, José Luis Martínez
Abstract
Collateral sensitivity (CS) is a trade-off of antibiotic resistance evolution that could be exploited to design strategies for treating bacterial infections. Clinical application of CS requires it to robustly emerge in different genomic backgrounds. In this study, we performed an analysis to identify robust patterns of CS associated with the use of ciprofloxacin in clinical isolates of P. aeruginosa presenting different mutational resistomes and including high-risk epidemic clones (ST111, ST175, and ST244). We demonstrate the robustness of CS to tobramycin and aztreonam and the potential application of this evolutionary observation to drive P. aeruginosa infections to extinction. Our results support the notion that the identification of robust CS patterns may establish the basis for developing evolutionary strategies to tackle bacterial infections, including those due to antibiotic-resistant pathogens.