Antibiotic resistance is an increasingly important global public health issue, as major opportunistic pathogens are evolving toward multidrug- and pan-drug resistance phenotypes. New antibiotics are thus needed to maintain our ability to treat bacterial infections. According to the WHO, carbapenem-resistant Acinetobacter, Enterobactericaeae, and Pseudomonas are the most critical targets for the development of new antibacterial drugs. An automated phenotypic screen was implemented to screen 634 synthetic compounds obtained in-house for both their direct-acting and synergistic activity. Fourteen percent and 10% of the compounds showed growth inhibition against tested Gram-positive and Gram-negative bacteria, respectively. The most active direct-acting compounds showed a broad-spectrum antibacterial activity, including on some multidrug-resistant clinical isolates. In addition, 47 compounds were identified for their ability to potentiate the activity of other antibiotics. Compounds of three different scaffolds (2-quinolones, phenols, and pyrazoles) showed a strong potentiation of colistin, some being able to revert colistin resistance in Acinetobacter baumannii.

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未聚焦的图书馆的屏幕识别出具有直接或协同抗菌活性的化合物。

随着主要的机会性病原体向多药耐药和全药耐药表型发展，抗生素耐药性已成为一个日益重要的全球公共卫生问题。因此，需要新的抗生素来维持我们治疗细菌感染的能力。根据世界卫生组织的说法，耐碳青霉烯的不动杆菌，肠杆菌和假单胞菌是开发新抗菌药物的最关键目标。实施了自动表型筛选，以筛选内部获得的634种合成化合物的直接作用和协同活性。分别有14％和10％的化合物对测试的革兰氏阳性细菌和革兰氏阴性细菌表现出生长抑制作用。活性最高的直接作用化合物具有广谱抗菌活性，包括一些耐多药临床分离株。此外，已鉴定出47种化合物增强其他抗生素活性的能力。三种不同支架（2-喹诺酮类，酚类和吡唑类）的化合物表现出很强的粘菌素增强能力，其中一些能够恢复鲍曼不动杆菌中的粘菌素抗性。