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

基本信息

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
项目类别：
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

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

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项目摘要

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.

抽象的该PPG项目2的目标是研究金黄色葡萄球菌必须微调其的假设中央代谢，以快速适应给定组织中可用的不同碳和氮源微环境。金黄色葡萄球菌具有在多种器官系统中定植或引起感染的能力人类宿主，因此必须适应每个小众内部的碳和氮源的变化。我们有将我们的研究集中在葡萄糖耗尽的葡萄球菌脓肿上，以及金黄色葡萄球菌如何持续使用次要碳源（例如氨基酸和肽）作为主要碳源。根据我们以前的数据，已经开发了一个模型，预测金黄色葡萄球菌裂解了特定的宿主蛋白促进运输通过寡肽转运蛋白（OPP-3）的肽。初步研究证明了肽运输诱导蛋白酶转录连接这两个基本过程。最后，我们记录了氨基当金黄色葡萄球菌在氨基酸上生长为唯一碳时，对生长至关重要的酸分解代谢途径来源。拟议的目的是建立在我们发展的模型的基础上，1）确定功能和受体动力学在小鼠感染模型中，四个金黄色葡萄球菌脯氨酸转运蛋白和脯氨酸转运的相关性； 2）研究肽转运与蛋白酶转录的诱导之间的关系； 3）审问丙酮酸产生氨基酸分解代谢和随后在生长过程中的重要性在缺乏葡萄糖的媒体中。