Abstract:Guanosine tetraphosphate (ppGpp)/guanosine pentaphosphate (pppGpp) is a signaling molecule in the bacterial stringent response, whose synthesis and hydrolysis are controlled by the synthesis and hydrolysis activities of proteins in the RelA/SpoT homologue (RSH) family. The (p)ppGpp-mediated stringent response enhanced bacterial adaptation to nutrient deprivation and antibiotic resistance. In recent years, (p)ppGpp has been found to associate with bacterial growth, cell division, and antibiotic synthesis, which was an important global regulator in the bacteria. (p)ppGpp has many target sites in the cell, which allow it to regulate DNA replication, transcription, cell cycle, ribosome biosynthesis, and the expression of antibiotic synthesis gene clusters. However, how (p)ppGpp controls transcription and other metabolic processes depends on the bacterial species, and (p)ppGpp regulates the same processes in different bacteria species through different mechanisms. Therefore, this manuscript reviewed the types of (p)ppGpp synthetic and hydrolytic enzymes, the mechanisms of (p)ppGpp regulation on microbial metabolism and the cell cycle, as well as the regulation mechanisms of antibiotic synthesis and tolerance, which lays the foundation for bacterial resistance and cell physiology researches.
