Ciprofloxacin resistance rapidly declines in nfxB defective clinical strains of Pseudomonas aeruginosa
Sara Hernando‐Amado, Pablo Laborda, Ruggero La Rosa, Søren Molin, Helle Krogh Johansen, José Luis Martínez
Abstract
Antibiotic-resistant bacteria could be tackled by identifying trade-offs of evolution, such as high fitness costs, which may be harnessed to force reversion to susceptibility. A decline in antimicrobial resistance can occur through compensatory mutations or by genetic reversion to the wild-type allele, which reduce fitness costs associated with resistance. We analyse here the impact of antibiotic-free environments on declining ciprofloxacin resistance in eight nfxB defective clinical strains of Pseudomonas aeruginosa spanning varied clone types and ciprofloxacin resistance levels. Ciprofloxacin resistance declines in just 100 generations, which is mainly caused by newly acquired mutations in the genes encoding the overproduced efflux pump MexCD-OprJ and not by the reversion of nfxB mutations of the parental strains. The rapid reversion of ciprofloxacin resistance in P. aeruginosa suggests the potential for reusing this essential antibiotic and underlines the need to implement evolution-based approaches against nfxB defective resistant mutant strains. Antimicrobial resistance can decline due to compensatory mutations or genetic reversions to wild-type alleles. Here, the authors analyse the decline of ciprofloxacin resistance in nfxB-defective Pseudomonas aeruginosa clinical isolates in antibiotic-free environments.