The critical roles of (p)ppGpp in homeostasis and antibiotic tolerance in Gram positive bacteria

摘要 细菌，从细菌到病原体，利用应激反应来维持细胞 在波动的环境中保持体内平衡，使细胞能够在营养缺乏、抗生素 治疗和宿主防御。细菌应激反应的一个非常保守的关键成分 是小信号分子（p）ppGpp（鸟苷四磷酸和五磷酸）。 （p）ppGpp可以在几乎所有细菌中产生，以介导应激抗性和适应。 （p）ppGpp对于代谢休眠的持久细胞的产生也是关键的， 抗生素难以杀死的。然而，（p）革兰氏阳性菌中的ppGpp调节， 包括许多人类病原体，知之甚少。建议的总体理由 我们的工作是解开革兰氏阳性菌中的（p）ppGpp调控，这将为革兰氏阳性菌的研究提供重要的参考。 深入了解细菌应激反应，抗生素耐受性和微生物之间的相互作用 和主机。

Abstract Bacteria, from commensals to pathogens, utilize stress responses to maintain cellular homeostasis in fluctuating environments, enabling cells to survive nutrient deprivation, antibiotic treatments and host defenses. A well conserved key component of the bacterial stress response is the small signaling molecule (p)ppGpp (guanosine tetraphosphate and pentaphosphate). (p)ppGpp can be produced in almost all bacteria to mediate stress resistance and adaptation. (p)ppGpp is also critical for the generation of persister cells that are metabolically dormant and refractory to killing by antibiotics. However, (p)ppGpp regulation in Gram-positive bacteria, including many human pathogens, is poorly understood. The overall rationale of the proposed work is to unravel (p)ppGpp regulation in Gram-positive bacteria, which will provide important insights into the bacterial stress response, antibiotic tolerance, and interactions between microbes and hosts.