Halogenated Phenazines that Potently Eradicate Biofilms, MRSA Persister Cells in Non-Biofilm Cultures, and Mycobacterium tuberculosis
Halogenated Phenazines that Potently Eradicate Biofilms, MRSA Persister Cells in Non-Biofilm Cultures, and Mycobacterium tuberculosis
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DOI：
10.1002/anie.201508155
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发表时间：
2015-12-01
影响因子：
16.6
通讯作者：
Huigens, Robert W., III
中科院分区：
文献类型：
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作者：
Garrison, Aaron T.;Abouelhassan, Yasmeen;Huigens, Robert W., III
传统抗生素对非复制细菌（例如生物膜内的细菌）无效。我们报道了一系列的卤代苯那嗪（HP），灵感来自海洋抗生素1，目标是持久性细菌。迄今为止，hp14对MRSA、MRSE和VRE生物膜（MBEC= 0.2-12.5 μ M）表现出最有效的生物膜根除活性，并在非生物膜培养中有效杀死MRSA持久性细胞。一线MRSA治疗，万古霉素和达托霉素，不能根除MRSA生物膜或非生物膜持续存在。hp13对缓慢生长的结核分枝杆菌（MIC= 3.13 μ M）显示出强大的抗菌活性，结核分枝杆菌是世界上细菌感染导致死亡的主要原因。HP类似物通过一种对哺乳动物细胞无毒的机制有效地靶向持久性细菌，并可能对慢性细菌感染的治疗产生重大影响。
Conventional antibiotics are ineffective against non-replicating bacteria (for example, bacteria within biofilms). We report a series of halogenated phenazines (HP), inspired by marine antibiotic 1, that targets persistent bacteria. HP 14 demonstrated the most potent biofilm eradication activities to date against MRSA, MRSE, and VRE biofilms (MBEC= 0.2-12.5 mu M), as well as the effective killing of MRSA persister cells in non-biofilm cultures. Frontline MRSA treatments, vancomycin and daptomycin, were unable to eradicate MRSA biofilms or non-biofilm persisters alongside 14. HP 13 displayed potent antibacterial activity against slow-growing M. tuberculosis (MIC= 3.13 mu M), the leading cause of death by bacterial infection around the world. HP analogues effectively target persistent bacteria through a mechanism that is non-toxic to mammalian cells and could have a significant impact on treatments for chronic bacterial infections.