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白藜芦醇作为诺氟沙星外排泵抑制剂及耐药调节剂在……中

Resveratrol as an Inhibitor of the NorA Efflux Pump and Resistance Modulator in .

作者信息

Santos Madalena, Santos Raquel, Soeiro Pedro, Silvestre Samuel, Ferreira Susana

机构信息

CICS-UBI-Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal.

出版信息

Antibiotics (Basel). 2023 Jul 10;12(7):1168. doi: 10.3390/antibiotics12071168.

Abstract

can exhibit resistance to various antibiotics. Among its resistance mechanisms, the active efflux of antibiotics can be seen as relevant. This study aimed to evaluate the ability of resveratrol to modulate norfloxacin resistance in . The antimicrobial activity of resveratrol was assessed using the broth microdilution method to determine the minimum inhibitory concentration (MIC). Then, the modulatory effect of resveratrol was evaluated using the MIC determination for the antibiotic or ethidium bromide in the presence and absence of resveratrol at a sub-MIC level. The MIC of norfloxacin against SA1199B (NorA-overexpressing strain) decreased 16-fold when in the presence of resveratrol, with a similar behavior being observed for ethidium bromide. An evaluation of the ethidium bromide accumulation was also performed, showing that in the presence of resveratrol, the SA1199B strain had augmented fluorescence due to the accumulation of ethidium bromide. Altogether, the results suggested that resveratrol may act by inhibiting NorA. These in vitro data were supported by docking results, with interactions between resveratrol and the NorA efflux pump predicted to be favorable. Our findings demonstrated that resveratrol may modulate norfloxacin resistance through the inhibition of NorA, increasing the effectiveness of this antibiotic against .

摘要

可表现出对多种抗生素的耐药性。在其耐药机制中,抗生素的主动外排被认为是相关的。本研究旨在评估白藜芦醇调节[具体菌株]对诺氟沙星耐药性的能力。采用肉汤微量稀释法评估白藜芦醇的抗菌活性以确定最低抑菌浓度(MIC)。然后,通过在存在和不存在亚MIC水平的白藜芦醇的情况下测定抗生素或溴化乙锭的MIC来评估白藜芦醇的调节作用。当存在白藜芦醇时,诺氟沙星对SA1199B(NorA过表达菌株)的MIC降低了16倍,溴化乙锭也观察到类似的情况。还进行了溴化乙锭积累的评估,结果表明在存在白藜芦醇的情况下,SA1199B菌株由于溴化乙锭的积累而荧光增强。总之,结果表明白藜芦醇可能通过抑制NorA起作用。这些体外数据得到对接结果的支持,预测白藜芦醇与NorA外排泵之间的相互作用是有利的。我们的研究结果表明,白藜芦醇可能通过抑制NorA来调节诺氟沙星耐药性,提高这种抗生素对[具体菌株]的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a117/10376492/6254d5ddcc56/antibiotics-12-01168-g001.jpg

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