Programmable molecular circuit discriminates multidrug-resistant bacteria

Recognizing multidrug-resistant (MDR) bacteria with high accuracy and precision from clinical samples has long been a difficulty. For reliable detection of MDR bacteria, we investigated a programmable molecular circuit called the Background-free isothermal circuital kit (BRICK). The BRICK method provides a near-zero background signal by integrating four inherent modules equivalent to the conversion, amplification, separation, and reading modules. Interference elimination is largely owing to a molybdenum disulfide nanosheets-based fluorescence nanoswitch and non-specific suppression mediated by molecular inhibitors. In less than 70 ​min, an accurate distinction of various MDR bacteria was achieved without bacterial lysis. The BRICK technique detected 6.73 ​CFU/mL of methicillin-resistant Staphylococcus aureus in clinical samples in a proof-of-concept trial. By simply reprogramming the sequence panel, such a high signal-to-noise characteristic has been proven in the four other superbugs. The proposed BRICK method can provide a universal platform for infection surveillance and environmental management thanks to its superior programmability.