用强代谢依赖型抗生素和弱代谢依赖型抗生素的组合消灭细菌持留菌。
Eradicating Bacterial Persisters with Combinations of Strongly and Weakly Metabolism-Dependent Antibiotics.
机构信息
Program in Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Machine Learning for Pharmaceutical Discovery and Synthesis Consortium, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Cell Chem Biol. 2020 Dec 17;27(12):1544-1552.e3. doi: 10.1016/j.chembiol.2020.08.015. Epub 2020 Sep 10.
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.
绝大多数杀菌抗生素对处于代谢抑制状态的细菌持久体（persisters）效果不佳。对这类细菌仍保持杀菌功能的分子通常对人体细胞有毒性，这限制了持久体感染的治疗选择。在这里，我们利用对代谢依赖性杀菌抗生素功效的深入了解，设计了既能杀菌又能使代谢活跃和持久细胞失活的抗生素组合，同时最大限度地减少所需的抗生素浓度。这些经过合理设计的抗生素组合有可能改善慢性和复发性感染的治疗效果。
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