Executive Summary : | Antimicrobial resistance (AMR) has become a global problem due to the empirical use of antibiotics which have led to the development of multidrug-resistant bacteria often referred to as “superbugs”. With no new antibiotics in the pipeline from the last 30 years, we need to encourage the preservation of currently available antimicrobial agents. Rapid antimicrobial susceptibility tests (AST) can help us to combat AMR by guiding clinicians and general practitioners to prescribe the right antibiotic and shift the paradigm from empirical to evidence-based treatment of infectious disease. Latest technology like VITEK 2 and MicroScan WalkAway automated system enables high-throughput testing of the microbes-antibiotic combination compared to traditional methods, but limitation lies in accuracy, cost, and time. VITEK 2 is based on fluorescence technology. The use of fluorescent tags in fluorescence-based technology suffers from problems related to aggregation-caused quenching (ACQ) at high concentrations, which limits its sensitivity. To overcome the ACQ effect of fluorescent dyes, a novel class of aggregation-induced emission (AIE) active luminescent material has emerged. AIE luminogens (AIEgens) are initially weakly emissive but become strongly emissive in aggregated forms. This “turn-on” characteristic of AIEgens provides a high signal-to-noise ratio, excellent photostability, high quantum yields, high sensitivity, and large Stoke’s shifts which makes them ideal scaffold for pathogen identification and AST. To tackle AMR, in this proposal, for the first time, we would like to develop a series of cationic AIE-active cyclometalated iridium(III) complexes for the identification of pathogens, screening of antibiotics, and evaluation of bacterial susceptibility (Figure 3 in other technical documents). Pathogens like bacteria and fungi are negatively charged on their outer surfaces. We would like to design AIE-active iridium probes that are positively charged and have hydrophobic units of varying lengths of alkane chain which would endow multivalent interaction with the pathogen to give a distinct fluorescence response. After identification of the pathogen, our next aim will be to perform AST and determine the minimum inhibitory concentration (MIC) for prescribing correct dose to the patient. For this, bacteria will be incubated with different antibiotics of varying concentrations and then treated with iridium probes. The change in the fluorescence intensity of iridium probes with an increase or decrease in bacterial population after antibiotic treatment will help us in antibiotic screening and getting MIC values. This holistic strategy would enable to develop a simple, rapid, sensitive, and wash-free array-based assay that could provide a reliable method for rapid identification of bacteria and AST to prescribe correct antibiotics within a very short time span. In this way, the proposed work would find widespread societal applications for tackling AMR. |