A novel bacterial protease and its involvement in wound infection

一种新型细菌蛋白酶及其与伤口感染的关系

• 批准号: 8971160
• 负责人: Gregory G Anderson
• 金额: $ 7.61万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8971160
• 关键词: Anti-Bacterial Agents; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Archaea; Bacteremia; Bacteria; Bacterial Infections; Bacterial Proteins; Bioinformatics; Burn injury; Cell physiology; Characteristics; Chronic; Colistin; Community Hospitals; Coupled; Cystic Fibrosis; Data; Degradation Pathway; Development; Diabetic ulcer; Disease Outbreaks; Drug Design; Drug Targeting; Eukaryota; Exhibits; Future; Genes; Goals; Heart; Hospitals; Human; Immune; In Vitro; Individual; Infection; Intensive Care Units; Investigation; Knowledge; Life; Link; Mantle Cell Lymphoma; Microbial Biofilms; Mission; Modeling; Molecular Machines; Morbidity - disease rate; Multi-Drug Resistance; Multiple Myeloma; Mutation; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Operative Surgical Procedures; Organ; Organism; Pathology; Pathway interactions; Patients; Peptide Hydrolases; Pharmaceutical Preparations; Process; Production; Proteins; Pseudomonas; Pseudomonas aeruginosa; Puncture wound; Qualifying; Reporting; Research; Resistance; Role; Sepsis; Series; Shapes; Siderophores; Stress; Structure; Surgical wound; System; Time; Toxin; Virulence; Virulence Factors; Work; Wound Healing; Wound Infection; base; cancer cell; human disease; in vitro activity; mortality; multicatalytic endopeptidase complex; new therapeutic target; novel; pathogen; protein degradation; protein misfolding; public health relevance; research study; response; stressor; wound

 DESCRIPTION (provided by applicant): Regulated degradation of proteins impacts all cellular processes and helps remove damaged or misfolded proteins, especially during cellular responses to various stressors. Proteasomes carry out the vast majority of the degradative functions in eukaryotes and archaea, but in bacteria are only found in the actinomycete lineage. This proposal aims to characterize a novel putative protein degradation machinery present in a number of bacteria, using the opportunistic pathogen Pseudomonas aeruginosa as a model. This will be achieved through two specific goals: 1. a thorough investigation of the structure and function of this putative protease. 2. Demonstration of its importance in processes that govern P. aeruginosa infection. Given the importance of this organism in the pathology of wound infections, among the numerous infections it causes, these studies will uncover bacterial protein degradation pathways that control infectivity and thereby impact normal wound healing. This approach will enable the identification of novel therapeutic targets for human disease states caused by pathogens, like P. aeruginosa, that rely on these protein degradation pathways.

 描述（由申请人提供）：蛋白质的调节降解影响所有细胞过程，并有助于去除受损或错误折叠的蛋白质，特别是在细胞对各种应激源的反应期间。蛋白酶体在真核生物和古细菌中执行绝大多数降解功能，但在细菌中仅在放线菌谱系中发现。该建议的目的是表征一种新的推定的蛋白质降解机制存在于一些细菌，使用机会致病菌铜绿假单胞菌作为模型。这将通过两个具体目标来实现：1。对这种假定的蛋白酶的结构和功能进行彻底的研究。2.证明其在控制铜绿假单胞菌感染的过程中的重要性。鉴于这种微生物在伤口感染病理学中的重要性，在它引起的众多感染中，这些研究将揭示控制感染性的细菌蛋白质降解途径，从而影响正常的伤口愈合。这种方法将能够识别由依赖于这些蛋白质降解途径的病原体（如铜绿假单胞菌）引起的人类疾病状态的新治疗靶点。