Multidrug evolutionary strategies to reverse antibiotic resistance.
Multidrug evolutionary strategies to reverse antibiotic resistance.
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DOI：
10.1126/science.aad3292
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Kishony R
中科院分区：
文献类型：
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作者：
Baym M;Stone LK;Kishony R
抗生素治疗有两个相互冲突的效果：抑制细菌生长的预期的即时效果和促进耐药性演变的不良的长期效果。尽管这些相反的结果似乎有着千丝万缕的联系，但最近的研究揭示了几种方法，可以通过组合抗生素来抑制细菌生长，同时与直觉相反，选择对抗耐药突变株。将治疗效果与耐药性风险脱钩可以通过利用药物之间的特定相互作用，以及对给定药物的耐药性突变可以调节这些相互作用或增加细菌对其他化合物的敏感性的方式来实现。尽管它们的实际应用需要进一步的开发和验证，并依赖于基因组诊断方面的进展，但这些发现提出了可能限制甚至逆转耐药性进化的新范式。
Antibiotic treatment has two conflicting effects: the desired, immediate effect of inhibiting bacterial growth and the undesired, long-term effect of promoting the evolution of resistance. Although these contrasting outcomes seem inextricably linked, recent work has revealed several ways by which antibiotics can be combined to inhibit bacterial growth while, counterintuitively, selecting against resistant mutants. Decoupling treatment efficacy from the risk of resistance can be achieved by exploiting specific interactions between drugs, and the ways in which resistance mutations to a given drug can modulate these interactions or increase the sensitivity of the bacteria to other compounds. Although their practical application requires much further development and validation, and relies on advances in genomic diagnostics, these discoveries suggest novel paradigms that may restrict or even reverse the evolution of resistance.