A cytoderm metabolic labeling AIEgen for rapid detection and intracellular ablation of Mycobacterium tuberculosis

Latent Mycobacterium tuberculosis (Mtb) shielded in macrophages is hard to detect and eradicate, causing lethal respiratory failure and systemic inflammation. Here, we synthesize an aggregation-induced emission luminogen (AIEgen) with metabolic labeling and in situ photodynamic scavenging functions via click chemistry. By participating in cytoderm peptidoglycan biosynthesis, the wash-free AIEgen presents quick (10 min) and selective metabolic labeling to live Mtb and obtains 50-fold better detection sensitivity of tuberculosis compared with acid-fast bacilli (AFBs). Notably, the AIEgen demonstrates accurate (>96%), sensitive (>96%), and specific (100%) clinical tuberculosis diagnosis using bronchoalveolar lavage fluid (BALF) and sputum samples. Upon low-power light irradiation, the AIEgen generates lethal-dose reactive oxygen species (ROS) to break the bacterial cytoderm and significantly improves the sensitivity of Mtb to rifampicin via photodynamic ablation. The AIEgen is a clinically oriented diagnostic for tuberculosis mass screening in regions with low income and a high tuberculosis burden and shows excellent potential for photodynamic ablation of drug-resistant tuberculosis.