Curcumin Reverses Antibiotic Resistance and Downregulates Shiga Toxin Expression in Enterohemorrhagic E. coli.

IF 2.9 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Martin Zermeño-Ruiz, Mirian Cobos-Vargas, Mauro Donaldo Saucedo-Plascencia, Rafael Cortés-Zárate, Leonardo Hernandez-Hernandez, Teresa Arcelia Garcia-Cobian, Teresa Estrada-Garcia, Araceli Castillo-Romero
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Abstract

Background: Enterohemorrhagic Escherichia coli (EHEC) is a considerable public health concern associated with several foodborne outbreaks of bloody diarrhea (BD) and the potentially lethal hemolytic uremic syndrome (HUS), the pathophysiology of which is attributable to the Shiga toxin (Stx) produced by this bacterium. In most patients, supportive treatment will be sufficient; however, in some cases, antibiotic treatment may be necessary. Most antibiotics are not recommended for EHEC infection treatment, particularly those that kill the bacteria, since this triggers the release of Stx in the body, inducing or worsening HUS. Azithromycin, which prevents the release of Stx and is a weaker inducer of the SOS system, has been successfully used to reduce EHEC shedding. It is necessary to identify compounds that eliminate EHEC without inducing Stx release. The use of natural compounds such as curcumin (CUR), a polyphenol derived from turmeric, has been highlighted as an alternative bactericidal treatment approach.

Objective: The objective of this study was to establish the effect of CUR and its interactions with selected antibiotics on resistant EHEC O157/H7/EDL933.

Methods: Bacterial cultures were exposed to CUR at three different concentrations (110, 220, and 330 µg/mL) and 1.2% DMSO, and the antimicrobial activity of CUR was assessed by measuring the optical density at 600 nm (OD600). The synergy of CUR and the antibiotics was determined with the FIC method. RT-PCR was performed to determine the expression levels of the blaCTX-M-15, catA1, acrAB-tolC stx2A, and stx2B genes.

Results: Our data indicate that CUR did not affect the growth of EHEC, but when combined with the antibiotics, it acted as a bacterial resistance breaker. Synergistic combinations of CUR and cefotaxime or chloramphenicol significantly reduced colony counts.

Conclusions: Our findings support the potential of CUR as a sensitizer or in combination therapy against EHEC.

姜黄素逆转肠出血性大肠杆菌的抗生素耐药性并下调志贺毒素表达。
背景:肠出血性大肠杆菌(EHEC)是一个相当大的公共卫生问题,与几次食源性血性腹泻(BD)暴发和潜在致命的溶血性尿毒症综合征(HUS)有关,其病理生理学可归因于该细菌产生的志贺毒素(Stx)。对于大多数患者,支持性治疗就足够了;然而,在某些情况下,抗生素治疗可能是必要的。大多数抗生素不推荐用于治疗肠出血性大肠杆菌感染,特别是那些杀死细菌的抗生素,因为这会引发体内Stx的释放,诱发或恶化溶血性尿毒综合征。阿奇霉素可以阻止Stx的释放,是一种较弱的SOS系统诱导性物质,已成功用于减少肠出血性大肠杆菌的脱落。有必要确定消除肠出血性大肠杆菌而不诱导Stx释放的化合物。使用天然化合物,如姜黄素(CUR),一种从姜黄中提取的多酚,已被强调为一种替代的杀菌治疗方法。目的:本研究的目的是确定CUR及其与选定抗生素相互作用对耐药肠出血性大肠杆菌O157/H7/EDL933的影响。方法:将细菌培养物暴露于三种不同浓度(110、220和330µg/mL)的CUR和1.2% DMSO中,通过测量600 nm (OD600)光密度来评估CUR的抗菌活性。用FIC法测定抗生素与CUR的协同作用。RT-PCR检测blaCTX-M-15、catA1、acrabb - tolc stx2A、stx2B基因的表达水平。结果:我们的数据表明,CUR不影响肠出血性大肠杆菌的生长,但当与抗生素联合使用时,它起到了细菌耐药的作用。CUR与头孢噻肟或氯霉素的协同联合显著减少菌落计数。结论:我们的研究结果支持CUR作为肠出血性大肠杆菌增敏剂或联合治疗的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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