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

(p)ppGpp 在革兰氏阳性菌体内平衡和抗生素耐受性中的关键作用

• 批准号: 10388549
• 负责人: Jue D. Wang
• 金额: $ 2.71万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10388549
• 关键词: Antibiotic Therapy; Antibiotics; Bacteria; Cells; Drug Tolerance; Environment; Generations; Gram-Positive Bacteria; Guanosine Pentaphosphate; Guanosine Tetraphosphate; Homeostasis; Host Defense; Mediating; Metabolic; Microbe; Nucleotides; Refractory; Regulation; Resistance; Role; Signal Transduction; Signaling Molecule; Stress; Work; antibiotic tolerance; antimicrobial; biological adaptation to stress; human pathogen; insight; nutrient deprivation; pathogen; prevent

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.

抽象的 细菌，从共生菌到病原体，利用应激反应来维持细胞 在波动的环境中保持体内平衡，使细胞能够在营养匮乏、抗生素的情况下生存 治疗和宿主防御。细菌应激反应中保存完好的关键组成部分 是小信号分子 (p)ppGpp（四磷酸鸟苷和五磷酸鸟苷）。 (p)ppGpp 几乎可以在所有细菌中产生，以介导应激抵抗和适应。 (p)ppGpp 对于代谢休眠和持久细胞的生成也至关重要 抗生素难以杀死。然而，革兰氏阳性菌中的 (p)ppGpp 调节， 包括许多人类病原体，人们对其知之甚少。拟议的总体理由 工作的目的是解开革兰氏阳性菌中的 (p)ppGpp 调节，这将提供重要的 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 和主持人。