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首页> 外文期刊>Antimicrobial agents and chemotherapy. >The Anthelmintic Drug Niclosamide Synergizes with Colistin and Reverses Colistin Resistance in Gram-Negative Bacilli
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The Anthelmintic Drug Niclosamide Synergizes with Colistin and Reverses Colistin Resistance in Gram-Negative Bacilli

机译：Anthelmintic药物Niclosamide与Colistin协同增量，并在革兰氏阴性杆菌中逆转Colistin抗性

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摘要

There is an urgent need for new therapies to overcome antimicrobial resistance especially in Gram-negative bacilli (GNB). Repurposing old U.S. Food and Drug Administration-approved drugs as complementary agents to existing antibiotics in a synergistic combination presents an attractive strategy. Here, we demonstrate that the anthelmintic drug niclosamide selectively synergized with the lipopeptide antibiotic colistin against colistin-susceptible but more importantly against colistin-resistant GNB, including clinical isolates that harbor the mcr-1 gene. Break-points for colistin susceptibility in resistant Gram-negative bacilli were reached in the presence of 1 mu g/ml (3 mu M) niclosamide. Reversal of colistin resistance was also observed in combinations of niclosamide and polymyxin B. Enhanced bacterial killing was evident for the combination, in comparison to colistin monotherapy, against resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae. Accumulating evidence in the literature, along with our results, strongly suggests the potential for the combination of niclosamide and colistin to treat colistin-resistant Gram-negative bacillary infections. Our finding is significant since colistin is an antibiotic of last resort for multidrug-resistant Gram-negative bacterial infections that are nonresponsive to conventional treatments. With the recent global dissemination of plasmid-encoded colistin resistance, the addition of niclosamide to colistin therapy may hold the key to overcome colistin resistance.
机译：迫切需要新的疗法来克服抗微生物抗性，特别是在革兰氏阴性杆菌（GNB）中。将旧的美国食品和药物管理局批准的药物作为协同组合中现有抗生素的互补药物具有吸引力的策略。在这里，我们证明了与脂肽抗生素菌氨酸的脂肪肽抗生素粘连蛋白酶易感，更重要的是对耐菌蛋白的GNB，包括患MCR-1基因的临床分离物。在1μg/ ml（3μm）Niclosamide存在下达到耐药革兰氏阴性杆菌中耐药素易感性的断裂点。还观察到核苷酸耐药性的逆转，与多糖蛋白酶B的组合中也观察到该组合的增强细菌杀死是显而易见的，与Colistin单疗法相比，抗性假单胞菌铜绿假单疗法，肺癌肺菌，肺炎氏菌，肺炎群岛，大肠杆菌和肠杆菌肝硬化。在文献中累积证据，以及我们的结果，强烈表明了尼卡洛胺和菌氨酸组合治疗耐药素革兰氏植物感染的潜力。我们的发现是显着的，因为Colistin是对常规治疗不尊重的多药抗革兰阴性细菌感染的最后手段的抗生素。随着最近的全局传播质粒编码的菌炎抗性，将Niclosamide加入Colistin疗法可能持有克服菌落抗性的关键。

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