Hernando-Amado Sara, Laborda Pablo, La Rosa Ruggero, Molin Søren, Johansen Helle Krogh, Martínez José Luis
Centro Nacional de Biotecnología. CSIC, Madrid, Spain.
Department of Clinical Microbiology 9301, Rigshospitalet, Copenhagen, Denmark.
Nat Commun. 2025 Jun 4;16(1):4992. doi: 10.1038/s41467-025-60330-2.
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.
通过识别进化的权衡因素，如高适应性成本，或许可以应对抗生素耐药菌，这些因素可能被利用来促使其恢复易感性。抗菌药物耐药性的下降可通过补偿性突变或基因回复到野生型等位基因来实现，这会降低与耐药性相关的适应性成本。我们在此分析了无抗生素环境对八株nfxB缺陷型铜绿假单胞菌临床菌株环丙沙星耐药性下降的影响，这些菌株涵盖了不同的克隆类型和环丙沙星耐药水平。环丙沙星耐药性在仅100代内就下降了，这主要是由编码过量产生的外排泵MexCD-OprJ的基因中新获得的突变引起的，而不是亲本菌株nfxB突变的回复。铜绿假单胞菌中环丙沙星耐药性的快速回复表明了重新使用这种重要抗生素的潜力，并强调了针对nfxB缺陷型耐药突变菌株实施基于进化的方法的必要性。
