Platinum Nanoparticles Prevent the Resistance of Pseudomonas aeruginosa to Ciprofloxacin and Imipenem: Mechanism Insights

Metal nanoparticles (MNPs) have recently gained extensive attention due to their broad-spectrum prospect, particularly in biomedical application. Here, we reveal that long-term exposure to platinum nanoparticles (Pt NPs) increases the susceptibility of Pseudomonas aeruginosa PAO1 to imipenem and ciprofloxacin. We exposed PAO1 to Pt NPs (a series of doses, varying from 0.125 to 35 μg/mL) for 60 days and characterized the evolved strains (ES) and compared with wild type (WT) to understand the mechanism of heightened sensitivity. We found that overexpression of oprD and downregulation of mexEF-oprN facilitate the intracellular accumulation of antibiotic, thus increasing susceptibility. Furthermore, loss-of-function mutations were discovered in regulators lasR and mexT. Cloning intact lasR from wild-type (WT) into ES slightly improves imipenem resistance. Strikingly, cloning mexT from WT into ES reverts the imipenem and ciprofloxacin resistance to the original level. Briefly, the increase of membrane permeability controlled by mexT made PAO1 greatly susceptible to imipenem and ciprofloxacin, and the decrease of quorum sensing mediated by lasR made PAO1 slightly susceptible to imipenem. Overall, these results reveal an antibiotic susceptibility mechanism from prolonged exposure to MNPs, which provides a promising approach to prevent antibiotic resistance.