Huggins William M, Barker William T, Baker James T, Hahn Nicholas A, Melander Roberta J, Melander Christian
Department of Chemistry, North Carolina State University, 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.
ACS Med Chem Lett. 2018 May 25;9(7):702-707. doi: 10.1021/acsmedchemlett.8b00161. eCollection 2018 Jul 12.
In the last 30 years, development of new classes of antibiotics has slowed, increasing the necessity for new options to treat multidrug resistant bacterial infections. Development of antibiotic adjuvants that increase the effectiveness of currently available antibiotics is a promising alternative approach to classical antibiotic development. Reports of the ability of the natural product meridianin D to modulate bacterial behavior have been rare. Herein, we describe the ability of meridianin D to inhibit biofilm formation of methicillin-resistant (MRSA) and to increase the potency of colistin against colistin-resistant and sensitive Gram-negative bacteria. Analogues were identified that are capable of inhibiting and dispersing MRSA biofilms and lowering the colistin MIC to below the CLSI breakpoint against , , and .
在过去30年里，新型抗生素的研发速度放缓，因此对于治疗多重耐药细菌感染的新选择的需求日益增加。开发能够提高现有抗生素疗效的抗生素佐剂是一种有前景的替代传统抗生素研发的方法。关于天然产物海人草素D调节细菌行为能力的报道很少。在此，我们描述了海人草素D抑制耐甲氧西林金黄色葡萄球菌（MRSA）生物膜形成以及增强黏菌素对耐黏菌素和敏感革兰氏阴性菌效力的能力。已鉴定出能够抑制和分散MRSA生物膜并将黏菌素的最低抑菌浓度降低至低于针对大肠杆菌、肺炎克雷伯菌和鲍曼不动杆菌的临床和实验室标准协会（CLSI）断点的类似物。
