Simultaneous Ultrasensitive Detection and Elimination of Drug-Resistant Bacteria by Cyclometalated Iridium(III) Complexes.
Ajay GuptaPuja PrasadShalini GuptaPijus K SasmalPublished in: ACS applied materials & interfaces (2020)
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.
Keyphrases
- drug resistant
- multidrug resistant
- loop mediated isothermal amplification
- gram negative
- acinetobacter baumannii
- public health
- label free
- antimicrobial resistance
- real time pcr
- staphylococcus aureus
- cell therapy
- stem cells
- dna damage
- risk assessment
- inflammatory response
- sensitive detection
- gold nanoparticles
- cancer therapy
- high resolution
- reactive oxygen species
- photodynamic therapy
- bone marrow
- heavy metals