Simultaneous Ultrasensitive Detection and Elimination of Drug-Resistant Bacteria by Cyclometalated Iridium(III) Complexes

Antimicrobial resistance has become a major threat to public health due to the rampant and empirical use of antibiotics. Rapid diagnosis of bacteria with the desired sensitivity and selectivity still, however, remains an open challenge. We report a special class of water-soluble metal-based aggregation-induced emission luminogens (AIEgens), namely, cyclometalated iridium­(III) polypyridine complexes of the type [Ir­(PQ)2(N^N)]Cl (1–3), where PQ = 2-phenylquinoline and N^N = 2,2′-bipyridine derivatives, that demonstrate dual capability for detection and elimination of drug-resistant bacteria in aqueous solutions. These AIEgens exhibit selective and rapid sensing of endotoxins, such as lipopolysaccharides (LPS) and lipoteichoic acid (LTA) released by the bacteria, with a detection limit in the lower nanomolar range. Targeting these naturally amplified biomarkers (approximately 1 million copies per cell) by iridium­(III) complexes induces strong AIE in the presence of different Gram-negative and Gram-positive bacteria including carbapenem-resistant A. baumannii (CRAB) and methicillin-resistant S. aureus (MRSA) at concentrations as low as 1.2 CFU/mL within 5 min in spiked water samples. Detection of bacteria by the complexes is also visible to the naked eye at higher (108 CFU/mL) cell concentrations. More notably, complexes 1 and 2 show potent antibacterial activity against drug-resistant bacteria with low minimum inhibitory concentrations (MICs) ≤ 5 μg/mL (1–4 μM) via ROS generation and cell membrane disintegrity. To the best of our knowledge, this work is the “first-in-class” example of a metal-based theranostic system that integrates selective, sensitive, rapid, naked-eye, wash-free, and real-time detection of bacteria using broad-spectrum antibiotics into a single platform. This dual capability of AIEgens makes them ideal scaffolds for monitoring bacterial contamination in aqueous samples and pharmaceutical applications.

由于抗生素的滥用与经验性使用，抗菌耐药性（antimicrobial resistance）已成为威胁公共卫生的重大隐患。然而，开发具备理想灵敏度与选择性的细菌快速诊断方法，仍是一项尚未解决的开放性难题。本研究报道了一类特殊的水溶性金属基聚集诱导发光发光体（aggregation-induced emission luminogens, AIEgens），即通式为[Ir(PQ)₂(N^N)]Cl（1~3）的环金属化铱(III)多吡啶配合物，其中PQ为2-苯基喹啉，N^N为2,2′-联吡啶衍生物；该类配合物在水溶液中可同时实现耐药菌的检测与清除。此类AIEgens可选择性快速识别细菌释放的内毒素，如脂多糖（lipopolysaccharides, LPS）与脂磷壁酸（lipoteichoic acid, LTA），检测下限处于低纳摩尔级别。铱(III)配合物可靶向结合这类天然高丰度生物标志物（每个细菌约含100万拷贝），在加标水样中，针对包括耐碳青霉烯类鲍曼不动杆菌（carbapenem-resistant A. baumannii, CRAB）与耐甲氧西林金黄色葡萄球菌（methicillin-resistant S. aureus, MRSA）在内的各类革兰氏阴性菌与革兰氏阳性菌，仅需5分钟即可在低至1.2 CFU/mL的菌浓度下触发强烈的AIE信号。当菌浓度较高（10⁸ CFU/mL）时，该配合物对细菌的检测结果也可通过肉眼直接观察。更值得关注的是，配合物1与2可通过产生活性氧（reactive oxygen species, ROS）并破坏细胞膜完整性，对耐药菌展现出强效抗菌活性，其最低抑菌浓度（minimum inhibitory concentrations, MICs）低至≤5 μg/mL（1~4 μM）。据我们所知，本工作是首个将对细菌的选择性、高灵敏度、快速、肉眼可视、无需洗涤且实时检测功能与广谱抗菌活性整合至单一平台的金属基诊疗系统范例。AIEgens的这种双重功能使其成为水溶液样品细菌污染监测与医药应用的理想骨架材料。