Nature’s signalling switches: turning bacteria into smart biosensors

Bacteria are experts at sensing and responding to their surroundings. They use built-in molecular switches called two-component systems (TCSs), which consist of two proteins: a sensor and a response regulator. These proteins work together to detect signals and trigger responses. Each protein has multiple functional parts, or domains. Key signalling domains are conserved across all bacterial species, making TCSs inherently modular. This modularity lets researchers exchange those domains, therefore reprogramming the system to detect new signals and deliver custom outputs—turning bacteria into smart biosensors. TCS-based biosensors are highly versatile and have a wide range of applications. In healthcare, for example, they can detect disease biomarkers and display visible readouts, such as colour changes. Challenges regarding specificity, sensitivity, safety, containment, and ethics remain; however, advances in genetic engineering continue to address these challenges and further establish modular TCS-based biosensors as powerful tools for medicine, sustainability, and industry.