posted on 2023-12-04, 20:06authored byZhiruo Zhou, Yulu Lian, Lin Zhu, Haibo Zhang, Zhangqiang Li, Meizhen Wang
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.