Antimicrobial resistance is an urgent threat to human health, and new antibacterial drugs are desperately needed, as are research tools to aid in their discovery and development. Vancomycin is a glycopeptide antibiotic that is widely used for the treatment of Gram-positive infections, such as life-threatening systemic diseases caused by methicillin-resistant Staphylococcus aureus (MRSA). Here we demonstrate that modification of vancomycin by introduction of an azide substituent provides a versatile intermediate that can undergo copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction with various alkynes to readily prepare vancomycin fluorescent probes.
View Article and Find Full Text PDFFluorescent probes are extensively applied as useful tools for imaging and determining dynamic processes in bacterial cells. In particular, antibiotic-derived fluorescent probes which can visualize the presence or the localization of antibiotics within bacteria through the monitoring of changes in fluorescence signal, are particularly useful. They form an emerging set of tools for studying the mode of action of their parent antibiotics and examining bacterial resistance and persistence, with the long-term goal of developing fresh approaches to the treatment of drug-resistant bacterial infections.
View Article and Find Full Text PDFWe report a flow-cytometry based method capable of detecting a range of analytes by monitoring the analyte-induced clustering of magnetic and fluorescent nanoparticles with flow cytometry. Using the dengue viral antigen (NS1) as an example, antibodies were conjugated to magnetic and fluorescent nanoparticles in a sandwich immunoassay format. These nanoparticles formed clusters when NS1 was present in a sample and the cluster formation was directly proportional to the concentration of antigen.
View Article and Find Full Text PDFReduced susceptibility to antimicrobials in Gram-negative bacteria may result from multiple resistance mechanisms, including increased efflux pump activity or reduced porin protein expression. Up-regulation of the efflux pump system is closely associated with multidrug resistance (MDR). To help investigate the role of efflux pumps on compound accumulation, a fluorescence-based assay was developed using fluorescent derivatives of trimethoprim (TMP), a broad-spectrum synthetic antibiotic that inhibits an intracellular target, dihydrofolate reductase (DHFR).
View Article and Find Full Text PDFNanoparticles used in biosensor applications often fail when deployed directly in complex biological fluids. This is due to surface fouling and interference from the large concentration of non-specific binders (proteins, lipids, nucleic acids and saccharides) in the matrix. We systematically investigate four orthogonal approaches for decorating nanoparticle surfaces with affinity probes and evaluate their performance in buffer and serum.
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