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A universal bacterial assay and kit for detecting and monitoring changes in concentration of a target analyte in solution. The assay relies on an engineered high affinity protein-based sensor with a detectable label that has high specificity to a target analyte, typically a ligand or metallated complex, and can be used to spectroscopically monitor interaction of the target analyte with a test bacterial strain. The sensors can be in the form of living, transport-deficient bacterial cells expressing the engineered high affinity protein, or in the form of purified proteins themselves. The system can further be used to screen candidate compounds for interference with the binding and uptake of such analytes by bacterial cells, which is useful in investigation of new classes of antibiotics.