Bacterial resistance is emerging as a global threat, stemming partially from continuous exposure of pathogens to antibiotics of sublethal concentrations. Thus, novel molecular approaches capable of inactivating antibiotics, which prevent their final build-up in the environment, are highly desirable. Here, we report a proof-of-principle demonstration of a mechanically new strategy for switchable control of antibiotic activity, which regulates drug uptake across the outer membrane of Gram-negative bacteria by externally triggered shape shifting of a short, covalently attached “tail”. The rationale behind this strategy is grounded in the size-selectivity of porin channels exploited by a large proportion of antibiotics for accessing intracellular targets, thus representing a general approach to control antibiotic availability in the environment which alleviates undue selection pressure for resistance.

中文翻译：

---

抗生素活性的可切换控制：变形的“尾巴”策略

细菌耐药性正在成为一种全球性威胁，部分原因是病原体持续暴露于致死浓度以下的抗生素。因此，非常需要能够使抗生素失活从而防止其在环境中最终积累的新型分子方法。在这里，我们报告了一种可机械控制抗生素活性的机械新策略的原理验证，该策略通过外部触发短而共价连接的“尾巴”的形状偏移来调节革兰氏阴性细菌外膜的药物吸收。 。此策略的基本原理是基于孔蛋白通道的大小选择性，而孔蛋白通道的选择性是由大量抗生素用于进入细胞内靶标而开发的，