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: 10665026
• 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/10665026
• 关键词: ATP Synthesis Pathway; Abscess; Acetates; Address; Alanine; Amino Acids; Aureolysin; Bacteremia; Binding; Biological Assay; Carbon; Catabolism; Citric Acid Cycle; Coenzyme A; Communities; 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; body system; derepression; 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 本PPG的项目#2的目标是研究金黄色葡萄球菌必须微调其 快速适应给定组织内不同碳源和氮源的中心代谢 微环境。S.金黄色葡萄球菌具有在宿主的多个器官系统中定殖或引起感染的能力。 因此必须适应每个生态位内不断变化的碳和氮源。我们有 我们的研究集中在葡萄球菌脓肿，这是葡萄糖耗尽，以及如何S。金黄色葡萄球菌持续 二级碳源如氨基酸和肽作为主要碳源。基于我们之前 数据，一个模型已经开发预测S。金黄色葡萄球菌切割促进转运的特异性宿主蛋白 寡肽转运蛋白（Opp-3）。初步研究表明， 诱导连接这两个基本过程的蛋白酶转录。最后，我们记录了氨基 酸分解代谢途径是生长的关键时，S。金黄色葡萄球菌以氨基酸作为唯一的碳源 源头提出的目标建立在我们的发展模型和1）确定功能和受体动力学 在四个S中。金黄色葡萄球菌脯氨酸转运蛋白和小鼠感染模型中脯氨酸转运的相关性; 2） 研究肽转运和蛋白酶转录诱导之间的关系;和3）询问 在生长过程中丙酮酸生成氨基酸催化剂和随后的乙酸生成的重要性 在缺乏葡萄糖的培养基中。