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姜黄素,一种抗多药耐药分支杆菌临床分离株的抗生素耐药破解剂。

Curcumin, an antibiotic resistance breaker against a multiresistant clinical isolate of Mycobacterium abscessus.

机构信息

Unit of Microbiology, Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, Ancona, Italy.

Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.

出版信息

Phytother Res. 2018 Mar;32(3):488-495. doi: 10.1002/ptr.5994. Epub 2017 Nov 29.

Abstract

Curcumin, a phenolic compound extracted from Curcuma longa, exerts multiple pharmacological effects, including an antimicrobial action. Mycobacterium abscessus, an environmental, nontuberculous, rapidly growing mycobacterium, is an emerging human pathogen causing serious lung infections and one of the most difficult to treat, due to its multidrug resistance and biofilm-forming ability. We wanted to evaluate the antimicrobial and antivirulence activity of curcumin and its ability to synergize with antibiotics against a clinical M. abscessus strain (29904), isolated from the bronchoaspirate of a 66-year-old woman admitted to hospital for suspected tuberculosis. Curcumin [minimum inhibitory concentrations (MIC) = 128 mg/L] was synergic (fractional inhibitory concentration index ≤0.5) with amikacin, clarithromycin, ciprofloxacin, and linezolid, to which strain 29904 showed resistance/intermediate susceptibility. Curcumin at 1/8 × MIC significantly reduced motility, whereas at 4 × MIC, it completely inhibited 4- and 8-day mature biofilms. Synergistic combinations of curcumin and amikacin induced a general reduction in microbial aggregates and substantial loss in cell viability. Disruption of 4- and 8-day biofilms was the main effect detected when curcumin was the predominant compound. The present findings support previous evidence that curcumin is a potential antibiotic resistance breaker. Curcumin, either alone or combined with antibiotics, could provide a novel strategy to combat antibiotic resistance and virulence of M. abscessus.

摘要

姜黄素是从姜黄中提取的一种酚类化合物,具有多种药理作用,包括抗菌作用。脓肿分枝杆菌是一种环境中非结核、快速生长的分枝杆菌,是一种新兴的人类病原体,可导致严重的肺部感染,并且由于其多药耐药性和生物膜形成能力,是最难治疗的病原体之一。我们想评估姜黄素的抗菌和抗毒力活性及其与抗生素协同作用的能力,以对抗从一名 66 岁女性支气管肺泡灌洗液中分离出的临床脓肿分枝杆菌(29904)株。姜黄素(最低抑菌浓度 [MIC] = 128 mg/L)与阿米卡星、克拉霉素、环丙沙星和利奈唑胺协同作用(部分抑菌浓度指数≤0.5),而 29904 株对这些药物表现出耐药/中介敏感性。姜黄素在 1/8 MIC 时显著降低了运动性,而在 4 MIC 时完全抑制了 4 天和 8 天成熟的生物膜。姜黄素与阿米卡星的协同组合导致微生物聚集体普遍减少,细胞活力显著降低。当姜黄素是主要化合物时,主要检测到破坏 4 天和 8 天生物膜的作用。目前的研究结果支持了先前的证据,即姜黄素是一种有潜力的抗生素耐药性破解剂。姜黄素单独或与抗生素联合使用,可能为对抗脓肿分枝杆菌的抗生素耐药性和毒力提供一种新策略。

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