Catabolism of peptides and amino acids by S. aureus

金黄色葡萄球菌对肽和氨基酸的分解代谢

• 批准号: 10198698
• 负责人: PAUL D FEY
• 金额: $ 38.13万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198698
• 关键词: ATP Synthesis Pathway; Abscess; Acetates; Address; Alanine; Amino Acids; Aureolysin; Bacteremia; Biological Assay; Carbon; Catabolism; Citric Acid Cycle; Cleaved cell; Coenzyme A; Community Hospitals; Critical Pathways; Data; Dependence; Disease; Endopeptidases; Environment; Generations; Genetic Transcription; Genus staphylococcus; Glucose; Glutamates; Glycine; Goals; Growth; Human; Infection; Kinetics; Length; Ligands; Link; Metabolic; Metabolic Pathway; Metabolism; Microbial Biofilms; Modeling; Mus; Nitrogen; Nosocomial Infections; Oligopeptides; Pathway interactions; Peptide Hydrolases; Peptide Transport; Peptides; Phosphate Acetyltransferase; Phosphorylation; Phosphotransferases; Process; Proline; Proteins; Publishing; Pyruvate; Reaction; Regulation; Serine; Source; Specificity; Staphylococcus aureus; Testing; Threonine; Tissues; base; body system; design; experimental study; extracellular; metabolomics; mouse model; mutant; pathogen; proline permease; receptor; staphylococcal protease; success

ABSTRACT The goal of project #2 of this PPG is to investigate the hypothesis that Staphylococcus aureus must fine-tune its central metabolism for rapid adaptation to different carbon and nitrogen sources available within a given tissue microenvironment. S. aureus has the ability to colonize or cause infection in a multitude of organ systems in the human host and therefore must adapt to changing carbon and nitrogen sources within each niche. We have focused our studies on a staphylococcal abscess, which is glucose depleted, and how S. aureus persists with secondary carbon sources such as amino acids and peptides as the major carbon source. Based on our previous data, a model has been developed predicting that S. aureus cleaves specific host proteins facilitating transport of peptides through oligopeptides transporters (Opp-3). Preliminary studies document that peptide transport induces protease transcription linking these two fundamental processes. Lastly, we have documented the amino acid catabolic pathways that are critical for growth when S. aureus is growing on amino acids as the sole carbon source. The proposed aims build upon our developing model and 1) determine the function and receptor kinetics of the four S. aureus proline transporters and relevance of proline transport in mouse models of infection; 2) Investigate the relationship between peptide transport and induction of protease transcription; and 3) Interrogate the importance of pyruvate generating amino acid catabolism and subsequent acetate generation during growth in media lacking glucose.

摘要 这个PPG项目#2的目标是调查金黄色葡萄球菌必须微调其 中枢代谢，可快速适应给定组织内的不同碳源和氮源 微环境。金黄色葡萄球菌能够在中国的许多器官系统中定植或引起感染 因此，它们必须适应每个生态位内不断变化的碳源和氮源。我们有 我们的研究集中在葡萄球菌脓肿，这是葡萄糖耗尽，以及金黄色葡萄球菌如何坚持 氨基酸、多肽等次要碳源为主要碳源。基于我们之前的 数据，已经建立了一个模型，预测金黄色葡萄球菌裂解特定的宿主蛋白促进运输 通过寡肽转运体(Opp-3)。初步研究证明，多肽运输 诱导连接这两个基本过程的蛋白水解酶转录。最后，我们已经记录了氨基 当金黄色葡萄球菌以氨基酸为唯一碳生长时，对生长至关重要的酸分解代谢途径 消息来源。提出的目标建立在我们的发育模型基础上，并1)确定功能和受体动力学 在小鼠感染模型中，四种金黄色葡萄球菌的Pro转运蛋白与Pro转运蛋白的相关性； 研究多肽转运与蛋白水解酶转录诱导的关系；3)询问 丙酮酸产生的氨基酸分解代谢和随后的醋酸盐产生在生长过程中的重要性 在缺乏葡萄糖的培养液中。