Switchable Control of Antibiotic Activity: A Shape-Shifting “Tail” Strategy

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.