Roles of two-component regulatory systems in Klebsiella pneumoniae: Regulation of virulence, antibiotic resistance, and stress responses

Klebsiella pneumoniae is an opportunistic pathogen belonging to the Enterobacteriaceae family, which is the leading cause of nosocomial infections. The emergence of hypervirulent and multi-drug resistant K. pneumoniae is a serious health threat. In the process of infection, K. pneumoniae needs to adapt to different environmental conditions, and the two-component regulatory system (TCS) composed of a sensor histidine kinase and response regulator is an important bacterial regulatory system in response to external stimuli. Understanding how K. pneumoniae perceives and responds to complex environmental stimuli provides insights into TCS regulation mechanisms and new targets for drug design. In this review, we analyzed the TCS composition and summarized the regulation mechanisms of TCSs, focusing on the regulation of genes involved in virulence, antibiotic resistance, and stress response. Collectively, these studies demonstrated that several TCSs play important roles in the regulation of virulence, antibiotic resistance and stress responses of K. pneumoniae. A single two-component regulatory system can participate in the regulation of several stress responses, and one stress response process may include several TCSs, forming a complex regulatory network. However, the function and regulation mechanism of some TCSs require further study. Hence, future research endeavors are required to enhance the understanding of TCS regulatory mechanisms and networks in K. pneumoniae, which is essential for the design of novel drugs targeting TCSs.