RstB/RstA: The Pleiotropic Two-Component System

Microorganisms utilize complex signal-regulating networks to adapt to environmental changes, and two-component system (TCS) plays a crucial role in bacterial sensing and response to environmental fluctuations. This article provides a comprehensive and in-depth multidimensional overview of the RstB/RstA TCS. The RstB/RstA TCS is capable of sensing a variety of external signals, including pH fluctuations, changes in Mg²⁺ concentration, antibiotics and osmotic pressure. And it regulates a variety of physiological processes, including motility, virulence factor expression, biofilm formation, and antibiotic resistance. RstB/RstA TCS might be a critical breakthrough for developing novel antimicrobial strategies to combat bacterial resistance. However, based on the PubMed database, few researches have been conducted on RstB/RstA, and knowledge on this TCS has not been reviewed. Furthermore, the precise regulatory mechanisms of the RstB/RstA system remain largely unexplored, especially in the ocean bacteria. This article integrates the key roles of the RstB/RstA TCS in environmental signal sensing and physiological function regulation. It mainly summarizes the structural composition, multifunctional roles, and regulatory mechanisms of the RstB/RstA system, especially its regulatory role in the marine pathogen Photobacterium damselae subsp. damselae (Pdd). In addition, we also discusse the current limitations of related research, and explore its great potential in the treatment of diseases affecting economically important fish species and human health. This work aims to provide a novel perspective for the study of TCSs in marine bacteria and to offer a theoretical foundation and future directions for further in-depth investigations of this regulatory system.