2.A.6.2.15
Multidrug efflux pump, MexCD-OprJ (exports β-lactams, fluoroquinolones, tetracycline, macrolides, chloramphenicol, biocides, including levofloxacin, carbenicillin, aztreonam, ceftazidime, cefepime, cefoperazone, piperacillin, erythromycin, azithromycin, chloramphenicol, etc.; Mao et al., 2002). Functions with MexC (MFP) and OprJ (OMF) as indicated above (Mao et al., 2002; Poole, 2008; Lorusso et al. 2022). MexCD-OprJ is one of four primary drug exporters in P. aeruginosa (Lorusso et al. 2022). Collateral sensitivity (CS) is an evolutionary trade-off traditionally linked to the mutational acquisition of antibiotic resistance (AR) (Hernando-Amado et al. 2023). However, AR can be temporally induced. Mutational acquisition of ciprofloxacin resistance leads to robust CS to tobramycin in pre-existing antibiotic-resistant mutants of Pseudomonas aeruginosa. Further, the strength of this phenotype is higher when nfxB mutants, over-producing the efflux pump MexCD-OprJ, are selected. Hernando-Amado et al. 2023 induced transient nfxB-mediated ciprofloxacin resistance by using the antiseptic dequalinium chloride. Notably, non-inherited induction of AR renders transient tobramycin CS in the analyzed antibiotic-resistant mutants and clinical isolates, including tobramycin-resistant isolates. Further, by combining tobramycin with dequalinium chloride we drive these strains to extinction. Our results support that transient CS could allow the design of new evolutionary strategies to tackle antibiotic-resistant infections, avoiding the acquisition of AR mutations on which inherited CS depends (Hernando-Amado et al. 2023). The type of quinolone resistance mechanism is related to the frequency of MDRP and the risk of MDRP incidence is highly dependent on the order of exposure to gentamicin and ciprofloxacin (Yasuda et al. 2023).