揭示慢性病药物作用背后的生物膜分子调控。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Bayan Taha Majid, Suha Ali Hussein, Shwan Kamal Rachid
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引用次数: 0

摘要

生物膜是一种复杂的微生物结构,可促进持续性感染的发展,尤其是在通过留置医疗器械造成的非医院环境中。传统抗生素往往无法有效治疗生物膜,因此,研究或设计能够成功减少和根除生物膜相关感染的非抗生素抗生物膜化合物至关重要。本研究试图重新利用抗高血压和抗血脂类慢性病药物,包括坎地沙坦西来替酯(CC)和熊去氧胆酸(UDCA),将其用作抗生物膜剂,以对抗金黄色葡萄球菌和粪肠球菌这两种感染性病原体。晶体紫(CV)染色法用于评估药物的抗生物膜活性。在使用不同浓度的 CC 和 UDCA 处理后,进行了实时聚合酶链反应(RT-PCR)以确定生物膜相关基因(金黄色葡萄球菌中的 icaA 和 icaR 以及粪肠球菌中的 fsrC 和 gelE)的转录水平。我们发现,浓度大于 1.5 µg/ml 的 CC 能显著抑制两种细菌分离物的生物膜形成(p < 0.005),而浓度大于 50 µg/ml 的 UDCA 能显著抑制两种细菌分离物的生物膜形成(p < 0.005)。有趣的是,当浓度低于人体每日用药剂量时,两种细菌分离物中生物膜相关基因的 mRNA 表达水平都有所下降。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unraveling the molecular regulation of biofilm underlying effect of chronic disease medications.

A biofilm is a complex microbial structure that promotes the progression of persistent infections, particularly in nosocomial settings via indwelling medical devices. Conventional antibiotics are often ineffective treatments for biofilms; hence, it is crucial to investigate or design non-antibiotic antibiofilm compounds that can successfully reduce and eradicate biofilm-related infections. This study was an attempt to repurpose chronic disease medications of the antihypertensive and antilipidemic drug classes, including candesartan cilexetil (CC) and ursodeoxycholic acid (UDCA), respectively, to be used as antibiofilm agents against the two infectious pathogens Staphylococcus aureus and Enterococcus faecalis. Crystal violet (CV) staining assay was used to evaluate the antibiofilm activity of the drugs. Real-time polymerase chain reaction (RT-PCR) was performed to determine the transcription levels of the biofilm-related genes (icaA and icaR in S. aureus and fsrC and gelE in E. faecalis) following treatment with different concentrations of CC and UDCA. we found that a concentration of greater than 1.5 µg/ml of CC significantly (p < 0.005) inhibited the biofilm formation of both bacterial isolates, and a concentration of greater than 50 µg/ml of UDCA significantly (p < 0.005) inhibited the biofilm formation of both bacterial isolates. Interestingly, the mRNA expression levels of biofilm-related genes were decreased in the two bacterial isolates at concentrations that were lower than the human pharmaceutical daily doses.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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