Trojan Antibiotics: New Weapons for Fighting Against Drug Resistance

Bacterial resistance has caused a global healthcare emergency due to the buildup of antibiotics in the environment. Novel approaches that enable highly efficient bactericide and auto inactivation are highly desired. Past researches mainly focused on the on-off bactericidal ability of antibiotics, which often displays unsatisfactory bactericidal efficiency. Herein, we report a Trojan antibiotic that considers the affinity of antibiotics to bacteria. A disguised host-guest supramolecule based on cucurbituril (CB[7]) and a bola-type azobenzene compound with glycosylamine heads at both ends is synthesized. This supramolecule has a surface fully decorated with sugar-like components, which are highly analogous to wall components of bacteria. This Trojan antibiotic is benign to a wide spectrum of bacteria at a weak basic pH of approximately 9.0 under daylight conditions. However, this antibiotic becomes a potent bactericide toward both Gram-negative and Gram-positive bacteria at pH 4.0 under 365 nm UV irradiation. The dual use of pH and UV light greatly enhances the efficiency of the bactericidal effect so that the 50% minimum inhibitory concentration (MIC₅₀) of the Trojan antibiotic is at least 10 times smaller than that of conventional drugs, and the removal of the UV source and reversal of pH automatically stop the antibacterial behavior, which prevents the buildup of active antimicrobial materials in the environment. We expect that the presented Trojan supramolecular strategy may open up a new paradigm in the fight against bacterial resistance.