Abstract:Histidine kinases are a crucial class of protein kinases involved in signal transduction pathways, playing a key role in bacterial responses to environmental stress. After more than 60 years of research, researchers have identified histidine kinases in a variety of bacteria. Bacterial histidine kinases are classified into 11 families, each encompassing multiple types. They accomplish the signal transduction process through one-step phosphorylation or multi-step cascading phosphorylation, thus regulating the expression of genes associated with stress responses and forming complex and diverse signal perception systems. This enables bacteria to effectively respond to temperature changes, adapt to antibiotic pressure, produce virulence, acclimate to acidic environments, and resistance to organic compounds. This review provides insights into the roles and mechanisms of histidine kinases, bacterial survival strategies and adaptability and facilitating the research on the application of histidine kinases in biology, medicine, and detection of small molecules.