Cell Chemical Biology ( IF 8.6 ) Pub Date : 2020-09-10 , DOI: 10.1016/j.chembiol.2020.08.015 Erica J Zheng 1 , Jonathan M Stokes 2 , James J Collins 3
The vast majority of bactericidal antibiotics display poor efficacy against bacterial persisters, cells that are in a metabolically repressed state. Molecules that retain their bactericidal functions against such bacteria often display toxicity to human cells, which limits treatment options for infections caused by persisters. Here, we leverage insight into metabolism-dependent bactericidal antibiotic efficacy to design antibiotic combinations that sterilize both metabolically active and persister cells, while minimizing the antibiotic concentrations required. These rationally designed antibiotic combinations have the potential to improve treatments for chronic and recurrent infections.
中文翻译:
根除具有强烈和弱代谢依赖的抗生素组合的细菌。
绝大多数杀菌抗生素对细菌持久性蛋白(处于代谢抑制状态的细胞)的功效不佳。保留针对此类细菌的杀菌功能的分子通常对人细胞表现出毒性,这限制了由持久性菌引起的感染的治疗选择。在这里,我们利用对新陈代谢依赖性杀菌抗生素功效的洞察力来设计能够对代谢活性和持久性细胞进行灭菌的抗生素组合,同时将所需的抗生素浓度降至最低。这些合理设计的抗生素组合具有改善慢性和复发性感染治疗的潜力。