(p)ppGpp——“魔斑”核苷酸在细菌中的研究进展

(p)ppGpp-“magic point” nucleotide in bacteria

摘要:

鸟苷四磷酸（guanosine tetraphosphate，ppGpp）/鸟苷五磷酸（guanosine pentaphosphate，pppGpp）是细菌严谨反应的信号分子，其合成和水解由Rel/SpoT同系物（RelA/SpoT homologue，RSH）家族的蛋白质合成和水解活性控制。（p）ppGpp介导的严谨反应能够提高细菌对营养匮乏的适应能力和抗生素抗性。近年来发现（p）ppGpp与细菌生长和细胞分裂、抗生素合成等都密切相关，是细胞内重要的全局调控因子。（p）ppGpp在细菌细胞中有许多靶点，使其可以调节DNA复制、转录、细胞周期、核糖体生物合成以及抗生素合成基因簇的表达。然而，（p）ppGpp如何控制转录和其他代谢过程取决于细菌种类，并在不同的微生物中通过不同的机制调节相同的过程。因此，本文通过综述（p）ppGpp的合成/水解酶的种类和调节机制，（p）ppGpp对微生物代谢调控机制、对细胞周期的影响机制，以及（p）ppGpp对抗生素合成和耐受性的调控机制，为细菌耐药性研究和细胞生理学研究奠定基础。

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.