Platinum Nanoparticles Prevent the Resistance of <i>Pseudomonas aeruginosa</i> to Ciprofloxacin and Imipenem: Mechanism Insights.

Abstract

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 <i>Pseudomonas aeruginosa</i> 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 <i>oprD</i> and downregulation of <i>mexEF-oprN</i> facilitate the intracellular accumulation of antibiotic, thus increasing susceptibility. Furthermore, loss-of-function mutations were discovered in regulators <i>lasR</i> and <i>mexT</i>. Cloning intact <i>lasR</i> from wild-type (WT) into ES slightly improves imipenem resistance. Strikingly, cloning <i>mexT</i> from WT into ES reverts the imipenem and ciprofloxacin resistance to the original level. Briefly, the increase of membrane permeability controlled by <i>mexT</i> made PAO1 greatly susceptible to imipenem and ciprofloxacin, and the decrease of quorum sensing mediated by <i>lasR</i> 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.