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将金诺芬重新用于对抗泌尿道致病性大肠杆菌生物膜。

Repurposing auranofin to combat uropathogenic Escherichia coli biofilms.

机构信息

Department of Medical Sciences, College of Medical Sciences, Soonchunhyang University, Asan, Republic of Korea.

Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan, Republic of Korea.

出版信息

J Appl Microbiol. 2019 Aug;127(2):459-471. doi: 10.1111/jam.14312. Epub 2019 Jun 6.

Abstract

AIMS

The aim of this study was to assess anti-biofilm and antimicrobial effects of auranofin, an anti-rheumatic agent, on uropathogenic Escherichia coli (UPEC) biofilm formation.

METHODS AND RESULTS

The minimum inhibitory concentration and biofilm inhibition concentration of auranofin against UPEC ranged from 24 to 32 μg ml . Biofilm eradication concentration and XTT reduction concentration of auranofin were found to be at 112 μg ml . Confocal laser scanning microscopy results confirmed that biofilm was inhibited by auranofin. These results indicate that auranofin possesses potent anti-biofilm and antimicrobial activities against UPEC. Effects of auranofin on type 1 fimbriae gene (fimH) and response regulator gene (rpoS) to stress were explored using quantitative real time-polymerase chain reaction. In addition, combination of auranofin and tetracycline showed synergistic effect.

CONCLUSIONS

These data indicate that auranofin has inhibitory effect on biofilm formation and synergistic effect on UPEC infection when it is combined with tetracycline.

SIGNIFICANCE AND IMPACT OF THE STUDY

Our study strongly suggest that auranofin is a promising alternative anti-biofilm and antimicrobial agent to prevent UPEC biofilm formation in UTIs. Auranofin already approved for human use have the advantage of being able to be put into clinical use relatively quickly.

摘要

目的

本研究旨在评估金诺芬(一种抗风湿药物)对尿路致病性大肠杆菌(UPEC)生物膜形成的抗生物膜和抗菌作用。

方法和结果

金诺芬对 UPEC 的最小抑菌浓度和生物膜抑制浓度范围为 24 至 32μg/ml。金诺芬的生物膜清除浓度和 XTT 还原浓度为 112μg/ml。共聚焦激光扫描显微镜结果证实金诺芬抑制了生物膜的形成。这些结果表明金诺芬对 UPEC 具有强大的抗生物膜和抗菌活性。使用定量实时聚合酶链反应探索了金诺芬对 1 型菌毛基因(fimH)和应激反应调节基因(rpoS)的影响。此外,金诺芬与四环素联合使用显示出协同作用。

结论

这些数据表明,金诺芬对生物膜形成具有抑制作用,与四环素联合使用对 UPEC 感染具有协同作用。

研究的意义和影响

我们的研究强烈表明,金诺芬是一种有前途的替代抗生物膜和抗菌剂,可预防 UTIs 中的 UPEC 生物膜形成。已被批准用于人类的金诺芬具有能够相对较快地投入临床使用的优势。

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