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植物化学物质作为尿路致病性大肠杆菌 FimH 拮抗剂的研究:体外和计算方法。

Phytochemicals As Uropathognic Escherichia Coli FimH Antagonist: In Vitro And In Silico Approach.

机构信息

Department of Biochemistry, Patna University, Patna, 800005, Bihar, India.

Synergy Diabetes Research Foundation, Patna-800023, Bihar, India.

出版信息

Curr Mol Med. 2018;18(9):640-653. doi: 10.2174/1566524019666190104104507.

DOI:10.2174/1566524019666190104104507
PMID:30608041
Abstract

BACKGROUND

Urinary tract infection (UTI) is caused by uropathogenic Escherichia coli (UPEC). The UPEC initiate pathogenesis by expressing type 1 pili, which attach to membrane receptors on the uroepithelial cells. Inhibition of attachment can provide a valuable target for prophylaxis in symptom-free milieu.

METHODS

The antibacterial efficacy of alcoholic, hydroalcoholic and aqueous extracts of four plants namely Achyranthes aspera, Andrographis paniculata, Artemissia vulgaris and Glycyrrhiza glabra was evaluated against seven isolated bacterial strains and procured E. coli (UTI89/UPEC) strain. Screening of isolated strains was based on morphological characteristics and biofilm forming ability followed by physiological and biochemical analysis.

RESULTS

The hydroalcoholic extracts of G. glabra at 50 μg/ml showed an impending antioxidant (DPPH) effect of 95.65% compared to ascorbic acid. The MIC values of all the plant extracts against selected bacterial strains ranged between 125 to 1000 μg/ml. In silico molecular docking performed to make out the antiadhesive role of 115 documented phytochemicals from selected plants identified quercetin-3-glucoside, ethyl caffeate, liquiritoside, liquiritin and isoliquiritigenin as potential phytochemicals. Molecular dynamics simulation performed by PTRAJ module of Amber11 package to monitor the stability of hydrogen bond showed that quercetin-3-glucoside and ethyl caffeate are potential phytochemicals as antiadhesive forming H-bonds with the FimH protein ligand.

CONCLUSIONS

Aforesaid phytochemicals demonstrate effective antibacterial activity through the anti-adhesion mechanism.

摘要

背景

尿路感染(UTI)是由尿路致病性大肠杆菌(UPEC)引起的。UPEC 通过表达 1 型菌毛引发发病机制,菌毛附着在上皮细胞的膜受体上。抑制附着可以为无症状环境中的预防提供有价值的目标。

方法

评估了四种植物即牛膝、穿心莲、艾蒿和甘草的醇提物、醇水提物和水提物对七种分离菌和获得的大肠杆菌(UTI89/UPEC)菌株的抗菌功效。根据形态特征和生物膜形成能力筛选分离株,然后进行生理生化分析。

结果

与抗坏血酸相比,甘草的水醇提取物在 50μg/ml 时显示出即将到来的抗氧化剂(DPPH)作用,为 95.65%。所有植物提取物对选定细菌株的 MIC 值在 125 至 1000μg/ml 之间。从选定植物中鉴定出 115 种有文献记载的植物化学物质,通过计算机分子对接来确定其抗粘附作用,鉴定出槲皮素-3-葡萄糖苷、咖啡酸乙酯、甘草苷、甘草素和异甘草素为潜在的植物化学物质。使用 Amber11 包的 PTRAJ 模块进行分子动力学模拟,以监测氢键的稳定性,结果表明,槲皮素-3-葡萄糖苷和咖啡酸乙酯是潜在的植物化学物质,因为它们与 FimH 蛋白配体形成氢键。

结论

上述植物化学物质通过抗粘附机制显示出有效的抗菌活性。

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