Targeting New Functions and Applications of Bacterial Two‐Component Systems

Two‐component signal transduction systems (TCSs) are regulatory systems widely distributed in eubacteria, archaea, and a few eukaryotic organisms, but not in mammalian cells. A typical TCS consists of a histidine kinase and a response regulator protein. Functional and mechanistic studies on different TCSs have greatly advanced the understanding of cellular phosphotransfer signal transduction mechanisms. In this concept paper, we focus on the His‐Asp phosphotransfer mechanism, the ATP synthesis function, antimicrobial drug design, cellular biosensors design, and protein allostery mechanisms based on recent TCS investigations to inspire new applications and future research perspectives. Two‐component signal transduction systems (TCSs) are widespread in bacteria, and crucial for their cellular processes. This concept paper focuses on His‐Asp phosphotransfer, the function of ATP synthesis, antimicrobial drug design, cellular biosensors, and protein allostery mechanisms based on recent TCS investigations, aiming to inspire new applications and future research directions.