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圆叶马蓝(Briq.)A. J. 帕顿中的萜类化合物改变铜绿假单胞菌PAO1中群体感应相关毒力因子的表达及生物膜的形成。

Terpenoids from Platostoma rotundifolium (Briq.) A. J. Paton Alter the Expression of Quorum Sensing-Related Virulence Factors and the Formation of Biofilm in Pseudomonas aeruginosa PAO1.

作者信息

Rasamiravaka Tsiry, Ngezahayo Jérémie, Pottier Laurent, Ribeiro Sofia Oliveira, Souard Florence, Hari Léonard, Stévigny Caroline, Jaziri Mondher El, Duez Pierre

机构信息

Laboratory of Plant Biotechnology, Université Libre de Bruxelles, rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium.

Laboratoire de Biotechnologie et Microbiologie, Département de Biochimie Fondamentale et Appliquée, Faculté des Sciences, Université d'Antananarivo (UA), BP 906, Antananarivo 101, Madagascar.

出版信息

Int J Mol Sci. 2017 Jun 14;18(6):1270. doi: 10.3390/ijms18061270.

Abstract

(Briq.) A. J. Paton aerial parts are widely used in Burundi traditional medicine to treat infectious diseases. In order to investigate their probable antibacterial activities, crude extracts from P. rotundifolium were assessed for their bactericidal and anti-virulence properties against an opportunistic bacterial model, PAO1. Whereas none of the tested extracts exert bacteriostatic and/or bactericidal proprieties, the ethyl acetate and dichloromethane extracts exhibit anti-virulence properties against PAO1 characterized by an alteration in quorum sensing gene expression and biofilm formation without affecting bacterial viability. Bioguided fractionation of the ethyl acetate extract led to the isolation of major anti-virulence compounds that were identified from nuclear magnetic resonance and high-resolution molecular spectroscopy spectra as cassipourol, β-sitosterol and α-amyrin. Globally, cassipourol and β-sitosterol inhibit quorum sensing-regulated and -regulatory genes expression in las and rhl systems without affecting the global regulators gacA and vfr, whereas α-amyrin had no effect on the expression of these genes. These terpenoids disrupt the formation of biofilms at concentrations down to 12.5, 50 and 50 µM for cassipourol, β-sitosterol and α-amyrin, respectively. Moreover, these terpenoids reduce the production of total exopolysaccharides and promote flagella-dependent motilities (swimming and swarming). The isolated terpenoids exert a wide range of inhibition processes, suggesting a complex mechanism of action targeting virulence mechanisms which support the wide anti-infectious use of this plant species in traditional Burundian medicine.

摘要

(布里奇)A. J. 帕顿指出,圆叶牵牛的地上部分在布隆迪传统医学中被广泛用于治疗传染病。为了研究其可能的抗菌活性,对圆叶牵牛的粗提物针对机会性细菌模型PAO1的杀菌和抗毒力特性进行了评估。尽管所测试的提取物均未表现出抑菌和/或杀菌特性,但乙酸乙酯和二氯甲烷提取物对PAO1表现出抗毒力特性,其特征在于群体感应基因表达和生物膜形成发生改变,而不影响细菌活力。对乙酸乙酯提取物进行生物导向分级分离,得到了主要的抗毒力化合物,通过核磁共振和高分辨率分子光谱确定为卡西波罗醇、β-谷甾醇和α-香树脂醇。总体而言,卡西波罗醇和β-谷甾醇抑制las和rhl系统中群体感应调节和调节基因的表达,而不影响全局调节因子gacA和vfr,而α-香树脂醇对这些基因的表达没有影响。这些萜类化合物分别在卡西波罗醇、β-谷甾醇和α-香树脂醇浓度低至12.5、50和50μM时破坏生物膜的形成。此外,这些萜类化合物减少了总胞外多糖的产生,并促进了鞭毛依赖性运动(游动和群游)。分离出的萜类化合物发挥了广泛的抑制作用,表明其作用机制复杂,靶向毒力机制,这支持了该植物物种在布隆迪传统医学中的广泛抗感染用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db8/5486092/9b5c6e74ad61/ijms-18-01270-g001.jpg

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