Phenotypic convergent evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic resistant mutants

In this work we describe a robust fosfomycin collateral sensitivity phenotype of Pseudomonas aeruginosa resistant mutants selected by antibiotics from different structural families. The underlying mechanism was the reduced expression of the genes encoding the peptidoglycan-recycling pathway, which preserves the peptidoglycan synthesis in situations where the de novo synthesis is blocked, and of fosA, encoding a fosfomycin-inactivating enzyme. Transcriptomic analysis of P. aeruginosa antibiotic resistant mutants (here dubbed Tgc5d, Tob5d and Caz5d) compared to wild-type PA14 strain