One-step light-up metabolic probes for in situ discrimination and killing of intracellular bacteria

Bacterial infections and the rise of antibiotic-resistance pose significant threats to public health, which calls for a profound change in diagnosis and treatment. Considering this, we develop two multi-functional light-up metabolic probes, namely TPEPy-Ala and TPAPy-Kdo, based on aggregation-induced emission (AIE) luminogens with photosensitizing properties. These AIE light-up probes can not only metabolically label both Gram-positive and Gram-negative bacteria with a high signal-to-noise contrast but also visualize the bacteria internalized in cells. Furthermore, these photosensitizing probes could in situ generate reactive oxygen species (ROS) upon light irradiation to effectively kill the intracellular bacteria. More importantly, both TPEPy-Ala and TPAPy-Kdo only exert minimal side effects on the host macrophages. This work presents a one-step light-up metabolic approach to discriminate and kill bacteria simultaneously with high specificity by utilizing their respective metabolic pathways.