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熊果酸共轭磁性纳米颗粒对多重耐药铜绿假单胞菌临床分离株的抗菌、抗生物膜和外排泵抑制作用增强

Enhanced antimicrobial, anti-biofilm, and efflux pump inhibitory effects of ursolic acid-conjugated magnetic nanoparticles against clinical isolates of multidrug-resistant Pseudomonas aeruginosa.

作者信息

Ghadimi Narges, Asadpour Leila, Mokhtary Masoud

机构信息

Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.

Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.

出版信息

Microb Pathog. 2025 Feb;199:107241. doi: 10.1016/j.micpath.2024.107241. Epub 2024 Dec 21.

DOI:10.1016/j.micpath.2024.107241
PMID:39716652
Abstract

OBJECTIVES

In the present study, we investigate the effect of FeO nanoparticles conjugated with ursolic acid (FeONPs@UA) on inhibiting the growth, biofilm-forming ability and efflux pump activity in clinical isolates of Pseudomonas aeruginosa with multiple drug resistance.

METHODS

Iron oxide NPs conjugated with ursolic acid (FeONPs@UA) were synthesized. Physicochemical features of the NPs were studied by FT-IR, XRD, EDAX, and TEM. The antibacterial and antibiofilm effects of FeONPs@UA against P. aeruginosa isolates were determined by broth microdilution and microtiter plate methods, respectively. The efflux pump inhibitory effect of FeONPs@UA was determined using Cartwheel method and through determining the expression level of efflux pump genes, including mexA and oprD in selected P. aeruginosa isolates treated with sub-MIC concentration of FeONPs@UA by real-time PCR.

RESULTS

In investigating the antimicrobial effect of FeONPs@UA, the MIC of these nanoparticles varied between 0.19 and 0.78 mg/mL and in the study of the anti-biofilm effect of FeONPs@UA, it caused a 68-75 % decrease in biofilm formation compared to the control. Moreover, in the Cartwheel test, the anti-efflux effect of these nanoparticles was confirmed at 1/4-MIC concentrations, and the expression of mexA and oprD genes was reduced in bacteria treated with FeONPs@UA compared to the control.

CONCLUSION

According to the results, the use of FeONPs@UA can provide a basis for the development of new treatments against drug-resistant bacteria in P. aeruginosa. This substance can improve the concentration of antibiotics in bacterial cells and increase their effectiveness by inhibiting the efflux in P. aeruginosa isolates.

摘要

目的

在本研究中,我们探究了熊果酸共轭的FeO纳米颗粒(FeONPs@UA)对多重耐药铜绿假单胞菌临床分离株生长、生物膜形成能力及外排泵活性的抑制作用。

方法

合成了熊果酸共轭的氧化铁纳米颗粒(FeONPs@UA)。通过傅里叶变换红外光谱(FT-IR)、X射线衍射(XRD)、能谱分析(EDAX)和透射电子显微镜(TEM)研究了纳米颗粒的物理化学特性。分别采用肉汤微量稀释法和微量滴定板法测定FeONPs@UA对铜绿假单胞菌分离株的抗菌和抗生物膜作用。采用车轮法并通过实时聚合酶链反应(PCR)测定在亚最小抑菌浓度(sub-MIC)的FeONPs@UA处理的选定铜绿假单胞菌分离株中外排泵基因(包括mexA和oprD)的表达水平,以此确定FeONPs@UA的外排泵抑制作用。

结果

在研究FeONPs@UA的抗菌作用时,这些纳米颗粒的最低抑菌浓度(MIC)在0.19至0.78毫克/毫升之间,在研究FeONPs@UA的抗生物膜作用时,与对照组相比,其生物膜形成减少了68%-75%。此外,在车轮试验中,这些纳米颗粒在1/4-MIC浓度下的抗外排作用得到证实,与对照组相比,用FeONPs@UA处理的细菌中mexA和oprD基因的表达降低。

结论

根据结果,FeONPs@UA的使用可为开发针对铜绿假单胞菌耐药菌的新疗法提供依据。该物质可提高抗生素在细菌细胞内的浓度,并通过抑制铜绿假单胞菌分离株的外排作用来提高其有效性。

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