Time-programmable drug dosing allows the manipulation, suppression and reversal of antibiotic drug resistance in vitro.
Time-programmable drug dosing allows the manipulation, suppression and reversal of antibiotic drug resistance in vitro.
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DOI：
10.1038/ncomms15589
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发表时间：
2017-06-08
影响因子：
16.6
通讯作者：
Cronin L
中科院分区：
文献类型：
--
作者：
Yoshida M;Reyes SG;Tsuda S;Horinouchi T;Furusawa C;Cronin L
人们尝试了多种药物策略来延长现有抗生素的疗效，但成效有限。在这里，我们表明，通过施用成对的抗生素并以开/关方式切换，可以在体外操纵多重耐药大肠杆菌的进化。使用多重细胞培养系统，我们发现在某些抗生素组合之间进行切换可以完全抑制对其中一种抗生素产生耐药性。利用这些数据，我们开发了一个简单的确定性模型，使我们能够预测该系统中多种药物进化的命运。此外，我们能够根据模型预测通过调节抗生素选择压力来逆转已建立的耐药性。我们的结果支持这样的观点：抗生素耐药性的发展可能通过连续更换药物来控制。目前尚不清楚涉及抗生素循环的策略是否可以有效控制抗生素耐药细菌的出现。在这里，吉田等人。研究表明，可以通过使用成对的抗生素并在它们之间切换来控制多重耐药细菌的体外进化。
Multi-drug strategies have been attempted to prolong the efficacy of existing antibiotics, but with limited success. Here we show that the evolution of multi-drug-resistant Escherichia coli can be manipulated in vitro by administering pairs of antibiotics and switching between them in ON/OFF manner. Using a multiplexed cell culture system, we find that switching between certain combinations of antibiotics completely suppresses the development of resistance to one of the antibiotics. Using this data, we develop a simple deterministic model, which allows us to predict the fate of multi-drug evolution in this system. Furthermore, we are able to reverse established drug resistance based on the model prediction by modulating antibiotic selection stresses. Our results support the idea that the development of antibiotic resistance may be potentially controlled via continuous switching of drugs. It is unclear whether strategies involving antibiotic cycling can efficiently control the emergence of antibiotic-resistant bacteria. Here, Yoshida et al. show that the evolution of multi-drug-resistant bacteria in vitro can be manipulated by administering pairs of antibiotics and switching between them.