C-di-AMP signaling in S. aureus

金黄色葡萄球菌中的 C-di-AMP 信号传导

• 批准号: 10089215
• 负责人: Joshua Woodward
• 金额: $ 54.86万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10089215
• 关键词: Adolescent; Antibiotic Resistance; Antibiotic Therapy; Antibiotic susceptibility; Bacteria; Bacterial Infections; Bacterial Physiology; Binding; Biochemical; Cells; Cessation of life; Chronic; Cladribine; Clinical; Cystic Fibrosis; Disease; Disease Progression; Enzymes; Exhibits; Gammaproteobacteria; Gene Expression Regulation; Growth; Human Genetics; Immune System Diseases; Immunity; Infection; Infectious Skin Diseases; Inflammation; Inflammatory; Influenza; Interferon-beta; Interferons; Laboratories; Link; Longitudinal cohort; Lung infections; Mediating; Mediator of activation protein; Metabolism; Modeling; Molecular; Monitor; Morbidity - disease rate; Multi-Drug Resistance; Mus; Nucleotides; Organism; Outcome; Pathogenesis; Pathologic; Pathology; Periodicity; Phenotype; Physiology; Pneumonia; Predisposition; Process; Production; Proteins; Proteobacteria; Pseudomonas aeruginosa; Pulmonary Fibrosis; Role; Second Messenger Systems; Signal Transduction; Signaling Molecule; Skin Tissue; Soft Tissue Infections; Staphylococcus aureus; Staphylococcus aureus infection; Study models; Surgical Wound Infection; Testing; Therapeutic Intervention; Thymidine; Tissues; Variant; Virulence; Wound Infection; acute infection; base; cell behavior; chronic infection; chronic wound; co-infection; cystic fibrosis patients; environmental change; genetic association; human disease; human morbidity; human mortality; immune activation; in vivo; insight; mortality; new therapeutic target; novel; pulmonary function decline; receptor; response; soft tissue; superinfection; thymidylate kinase; tissue culture

Abstract Staphylococcus aureus is a leading cause of human morbidity and mortality, causing infection of the skin and soft tissues, post-surgical wounds, and lung infection among influenza and cystic fibrosis patients. Widespread multi-drug resistance has made eradication of S. aureus increasingly challenging, necessitating a deeper understanding of the physiology and pathogenesis associated with these organisms. A key aspect of bacterial survival and adaptation to altered environmental conditions is the ability to rapidly alter cellular behavior through second messenger signal transduction. C-di-AMP has recently emerged as a key regulator of bacterial physiology, pathogenesis, and immune activation. In the context of S. aureus, we believe that c- di-AMP produced by S. aureus has three important roles; (i) as a signaling molecule that mediates S. aureus metabolism and antibiotic resistance, (ii) as a bacterial PAMP that promotes pathological inflammation and host susceptibility to bacterial infection, and (iii) as a mediator of inter-bacterial signaling that alters the outcome of co-infections. Findings from these studies may have significant impacts on the course of antibiotic therapy during S. aureus infection and may uncover a novel target to eradicate recalcitrant S. aureus and the inflammation itpromotes.

摘要 金黄色葡萄球菌（Staphylococcus aureus）是人类发病率和死亡率的主要原因，其引起细菌感染。 皮肤和软组织，手术后伤口，以及流感和囊性肺炎中的肺部感染 纤维化患者广泛存在的多重耐药使得根除沙门氏菌成为可能。金黄色 越来越具有挑战性，需要更深入地了解生理学， 与这些生物体有关的致病机制。细菌生存和适应的一个关键方面 改变环境条件的能力是通过第二次快速改变细胞行为的能力， 信使信号转导C-di-AMP最近已成为细菌生长的关键调节剂， 生理学、发病机理和免疫激活。在S. aureus我们相信c- 二磷酸腺苷（di-AMP）是S.金黄色葡萄球菌有三个重要作用：（i）作为一种信号分子， S.金黄色葡萄球菌代谢和抗生素抗性，（ii）作为细菌PAMP，促进 病理性炎症和宿主对细菌感染的易感性，和（iii）作为 细菌间的信号传导改变了合并感染的结果。这些研究的结果可能 对S.金黄色葡萄球菌感染， 发现了一个新的目标，以消除柠檬酸S。金黄色葡萄球菌及其引发的炎症。