Open AccessMutational background influencesP. aeruginosaciprofloxacin resistance evolution but preserves collateral sensitivity robustness
Author(s) -
Sara Hernando-Amado,
Pablo Laborda,
José Ramón Valverde,
José Luis Martínez
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2109370119
Subject(s) - aztreonam , tobramycin , ciprofloxacin , antibiotic resistance , collateral damage , biology , pseudomonas aeruginosa , antibiotics , microbiology and biotechnology , antibiotic sensitivity , mutant , genetics , bacteria , gentamicin , gene , imipenem , criminology , sociology
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 byPseudomonas 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.