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鞣酸对 norA 基因表达和 NorA 外排泵的抑制作用。

Inhibition of the norA gene expression and the NorA efflux pump by the tannic acid.

机构信息

Laboratory of Microbiology and Molecular Biology (LMBM), Department of Biological Chemistry/CCBS/URCA, Recife, Brazil.

Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

出版信息

Sci Rep. 2023 Oct 13;13(1):17394. doi: 10.1038/s41598-023-43038-5.

Abstract

The NorA efflux pump of Staphylococcus aureus is known to play a major role in the development of resistance against quinolone drugs by reducing their concentration inside target pathogens. The objective of this study was to evaluate the ability of tannic acid to inhibit the gene expression of the NorA efflux pump in Staphylococcus aureus and to evaluate the in silico effect on the pump. Efflux pump inhibition was evaluated by fluorimetry. The checkerboard method evaluates the effect of the test substance in combination with an antimicrobial at different concentrations. To gene expression evaluation NorA the assay was performed using: a sub-inhibitory concentration preparation (MIC/4) of the antibiotic; a sub-inhibitory concentration preparation (MIC/4) of the antibiotic associated with tannic acid at a sub-inhibitory concentration (MIC/4). In this study, docking simulations were performed by the SWISSDOCK webserver. The ability of tannic acid to inhibit the NorA efflux pump can be related to both the ability to inhibit the gene expression of this protein, acting on signaling pathways involving the ArlRS membrane sensor. As well as acting directly through direct interaction with the NorA protein, as seen in the approach and in silico and in vitro per checkerboard method and fluorimetry of bromide accumulated in the cell.

摘要

金黄色葡萄球菌的 NorA 外排泵已知在降低喹诺酮类药物在靶病原体内部的浓度方面发挥主要作用,从而导致对喹诺酮类药物的耐药性发展。本研究的目的是评估单宁酸抑制金黄色葡萄球菌 NorA 外排泵基因表达的能力,并评估其对泵的计算影响。通过荧光法评估外排泵抑制作用。棋盘法评估测试物质与不同浓度的抗菌药物联合使用的效果。为了评估 NorA 的基因表达,使用以下方法进行了检测:抗生素的亚抑制浓度制剂(MIC/4);抗生素的亚抑制浓度制剂(MIC/4)与单宁酸的亚抑制浓度(MIC/4)联合使用。在这项研究中,通过 SWISSDOCK 网络服务器进行了对接模拟。单宁酸抑制 NorA 外排泵的能力可能与抑制该蛋白基因表达的能力有关,其作用于涉及 ArlRS 膜传感器的信号通路。以及通过与 NorA 蛋白的直接相互作用直接起作用,正如棋盘法和体外溴化物积累检测法以及荧光法所表明的那样。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ac5/10575910/3a22ffc2c8ef/41598_2023_43038_Fig1_HTML.jpg

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