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: 10158497
• 负责人: Jue D. Wang
• 金额: $ 37.31万
• 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/10158497
• 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.

摘要