biostudies-literatureWardell SJTUniversity of OtagoManatu Hauora | Health Research Council of New ZealandAAC.01619-19https://www.ebi.ac.uk/biostudies/studies/S-EPMC6879238biostudies-literatureUnknown63(12)<i>Pseudomonas aeruginosa</i> is an opportunistic pathogen that causes a wide range of acute and chronic infections. An increasing number of isolates have mutations that make them antibiotic resistant, making treatment difficult. To identify resistance-associated mutations we experimentally evolved the antibiotic sensitive strain <i>P. aeruginosa</i> PAO1 to become resistant to three widely used anti-pseudomonal antibiotics, ciprofloxacin, meropenem and tobramycin. Mutants could tolerate up to 2048-fold higher concentrations of antibiotic than strain PAO1. Genome sequences were determined for thirteen mutants for each antibiotic. Each mutant had between 2 and 8 mutations. For each antibiotic at least 8 genes were mutated in multiple mutants, demonstrating the genetic complexity of resistanAntimicrobial agents and chemotherapyA large-scale whole-genome comparison shows that experimental evolution in response to antibiotics predicts changes in naturally evolved clinical <i>Pseudomonas aeruginosa</i>.PMC687923817/372Lamont ILPatrick WMWardell SJTMartin LWRehman AWinstanley CfalseA large-scale whole-genome comparison shows that experimental evolution in response to antibiotics predicts changes in naturally evolved clinical <i>Pseudomonas aeruginosa</i>.<i>Pseudomonas aeruginosa</i> is an opportunistic pathogen that causes a wide range of acute and chronic infections. An increasing number of isolates have mutations that make them antibiotic resistant, making treatment difficult. To identify resistance-associated mutations we experimentally evolved the antibiotic sensitive strain <i>P. aeruginosa</i> PAO1 to become resistant to three widely used anti-pseudomonal antibiotics, ciprofloxacin, meropenem and tobramycin. Mutants could tolerate up to 2048-fold higher concentrations of antibiotic than strain PAO1. Genome sequences were determined for thirteen mutants for each antibiotic. Each mutant had between 2 and 8 mutations. For each antibiotic at least 8 genes were mutated in multiple mutants, demonstrating the genetic complexity of resistan2019-01-01T00:00:00Z2019 Sep2026-05-05T02:20:55.958Z2020-05-24T07:08:34ZS-EPMC68792383157039710.1128/AAC.01619-1910.1128/aac.01619-19