Identification of drug-resistance determinants in a clinical isolate of Pseudomonas aeruginosa by high-density transposon mutagenesis

Pseudomonas aeruginosa is one of the most frequent causes of nosocomial infections, especially in immunocompromised patients, and the spread of multidrug-resistant strains is continuously increasing. Therefore, novel strategies for therapy are urgently required. In this approach we postulated that antimicrobial resistance can be reversed by targeting non-essential genes that are essential in the presence of therapeutic concentrations of antibiotics. A high-density transposon mutant library in a multidrug-resistant Pseudomonas aeruginosa bloodstream isolate (ID40) was generated and the depletion of transposon mutants upon exposure of cefepime or meropenem was measured leading to the identification of the common resistome for cefepime and meropenem.