Bacterial second messenger c-di-GMP: Emerging functions in stress resistance

In natural environments, bacteria constantly encounter various stressful conditions, including nutrient starvation, toxic chemicals, and oxidative stress. The ability to adapt to these adverse conditions is crucial for bacterial survival. Frequently, bacteria utilize nucleotide signaling molecules such as cyclic diguanylate (c-di-GMP) to regulate their behaviors when encounter stress conditions. c-di-GMP is a ubiquitous bacterial second messenger regulating the transition between the planktonic state and biofilm state. An essential feature of biofilms is the production of extracellular matrix that covers bacterial cells and offers a physical barrier protecting the cells from environmental assaults. Beyond that, accumulating evidences have demonstrated that changes in the environment, including stress stimuli, cause the alteration of intracellular levels of c-di-GMP in bacterial cells, which is immediately sensed by a variety of downstream effectors that induce an appropriate stress response. In this review, we summarize recent research on the role of c-di-GMP signaling in bacterial responses to diverse stress conditions.