呋喃酮,预防表皮葡萄球菌生物膜感染的潜在药物?

Furanones, potential agents for preventing Staphylococcus epidermidis biofilm infections?

作者信息

Lönn-Stensrud Jessica, Landin Maria A, Benneche Tore, Petersen Fernanda C, Scheie Anne Aamdal

机构信息

Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.

出版信息

J Antimicrob Chemother. 2009 Feb;63(2):309-16. doi: 10.1093/jac/dkn501. Epub 2008 Dec 20.

Abstract

OBJECTIVES

Staphylococcus epidermidis is often associated with biofilm infections related to medical implants. The aim of the present study was to find furanones that decrease biofilm formation without irritative or genotoxic effects, or effects on S. epidermidis growth.

METHODS

After screening including bioluminescence and biofilm assays, 2 furanones out of 11 were chosen for further studies. MIC values of the two furanones were established to determine whether biofilm inhibition effects were ascribed to inhibition of bacterial growth. To further investigate interference with communication, the effect of the furanones was tested in the presence of the autoinducer-2 precursor (S)-4,5-dihydroxy-2,3-pentanedione. The furanones were tested for possible irritative effects by the Hen's egg test chorioallantoic membrane procedure. Finally, potential genotoxic effects in mice were assessed by a membrane array, and effects on global gene expression were investigated by using a microarray representing 30,000 genes of the mouse genome.

RESULTS

From the bioluminescence assay, 4 furanones out of 11 were chosen for further biofilm analyses. Biofilm formation by S. epidermidis was significantly decreased by the four furanones tested at concentrations not affecting microbial growth. Two furanones were chosen for further studies: one that decreased biofilm statistically more than the others and one containing two bromo substituents. The two furanones were found to be non-irritative and non-genotoxic at the concentrations used.

CONCLUSIONS

Furanones may inhibit biofilm formation through interference with quorum sensing and thus represent promising agents for protecting surfaces from being colonized by S. epidermidis.

摘要

目的

表皮葡萄球菌常与医疗植入物相关的生物膜感染有关。本研究的目的是寻找能减少生物膜形成且无刺激或遗传毒性作用,也不影响表皮葡萄球菌生长的呋喃酮。

方法

经过包括生物发光和生物膜检测在内的筛选后,从11种呋喃酮中选择了2种进行进一步研究。确定这两种呋喃酮的最低抑菌浓度(MIC)值,以判断生物膜抑制作用是否归因于对细菌生长的抑制。为了进一步研究对群体感应的干扰,在自诱导物-2前体(S)-4,5-二羟基-2,3-戊二酮存在的情况下测试呋喃酮的作用。通过鸡胚绒毛尿囊膜试验检测呋喃酮可能的刺激作用。最后,通过膜阵列评估小鼠体内潜在的遗传毒性作用,并使用代表小鼠基因组30000个基因的微阵列研究对整体基因表达的影响。

结果

从生物发光检测中,选择了11种呋喃酮中的4种进行进一步的生物膜分析。所测试的4种呋喃酮在不影响微生物生长的浓度下能显著减少表皮葡萄球菌生物膜的形成。选择了2种呋喃酮进行进一步研究:一种在统计学上比其他的更能减少生物膜形成,另一种含有两个溴取代基。在所使用的浓度下,发现这两种呋喃酮无刺激性和遗传毒性。

结论

呋喃酮可能通过干扰群体感应来抑制生物膜形成,因此是保护表面不被表皮葡萄球菌定植的有前景的药物。

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