Effect of Arginine Metabolism on Biofilm Formation in the Staphyloccoci

精氨酸代谢对葡萄球菌生物膜形成的影响

基本信息

批准号：
7750237
负责人：
PAUL D FEY
金额：
$ 29.67万
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 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7750237
关键词：
Address Adherence Aerobic Ammonia Antibiotic Therapy Arginine Arginine deiminase Bacteremia Biocompatible Materials Catabolism Cavia Cells DNA Data Development Disease Environment Foreign Bodies Gene Cluster Gene Expression Gene Fusion Genes Genetic Genus staphylococcus Glucose Growth Healthcare Heterogeneity Immune system Infection Instruction Island Lead Link Maintenance Metabolic Metabolism Microbial Biofilms Minor Modeling Morbidity - disease rate Mus Nitric Oxide Operon Oryctolagus cuniculus Pathogenicity Island Pathway interactions Pattern Physiological Predisposition Proteins Regulation Relative (related person)Reporter Genes Role Societies Staphylococcus aureus Staphylococcus epidermidis Testing Transcriptional Regulation Virulence base burden of illness cost design extracellular mortality mutant novel pH Homeostasis polysaccharide intercellular adhesin research study

Address Adherence Aerobic Ammonia Antibiotic Therapy Arginine Arginine deiminase Bacteremia Biocompatible Materials Catabolism Cavia Cells DNA Data Development Disease Environment Foreign Bodies Gene Cluster Gene Expression Gene Fusion Genes Genetic Genus staphylococcus Glucose Growth Healthcare Heterogeneity Immune system Infection Instruction Island Lead Link Maintenance Metabolic Metabolism Microbial Biofilms Minor Modeling Morbidity - disease rate Mus Nitric Oxide Operon Oryctolagus cuniculus Pathogenicity Island Pathway interactions Pattern Physiological Predisposition Proteins Regulation Relative (related person)Reporter Genes Role Societies Staphylococcus aureus Staphylococcus epidermidis Testing Transcriptional Regulation Virulence base burden of illness cost design extracellular mortality mutant novel pH Homeostasis polysaccharide intercellular adhesin research study

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项目摘要

Staphylococci are a major burden on our society causing significant morbidity, mortality, and increased cost in healthcare. Increasing this disease burden is their ability to form biofilms on biomaterials resulfing in increased tolerance to anfibiofics and action of the immune system. Further study on the development and maturation of staphylococcal biofilms may lead to novel therapeufics that lead to their disruption. Staphylococcal biofilms are known to display spatial heterogeneity containing several physiological states including aerobic and anaerobic regions. Maintenance of these physiological states is imperative to the development of a mature biofilm. It is hypothesized that arginine catabolism is crucial for the development and maturation of anaerobic regions within both a Staphylococcus aureus and S. epidermidis biofilm. In fact, several backgrounds of both S. aureus and S. epidermidis contain two complete copies of the arginine deiminase (ADI) operon, one of which is acquired on a pathogenicity island. The ADI operon synthesizes proteins which catabolize arginine resulfing in ATP and ammonia. Within certain microniches of a biofllm environment, the resulting ATP can be used for metabolic purposes whereas the ammonia may be used for pH homeostasis. Studies demonstrate that arginine metabolism is induced during biofilm development and that the acquired (i.e. from pathogenicity island) ADI operon is most transcriptionally active as the biofilm matures. The importance of arginine metabolism will be studied by first exploring the regulatory role of ArcR, a known regulator of ADI expression, during biofilm growth. It is hypothesized that maximal inducfion of the acquired ADI operon occurs during biofilm growth and that Induction under these conditions is ArcR- dependent Secondly, through the use of fluorescent gene fusions, we will examine the temporal and spafial pattern of ADI gene expression within a S. epidermidis and S. aureus biofilm and compare those data to known anaerobic and aerobic regions of a biofilm. Lasfiy, through a mouse foreign body infection model, the relative virulence of ADI mutants in comparison to wild type S. aureus and S. epidermidis w'\\\ be determined. Suscepfibility of ADI mutants to anfibiotics will be tested in a guinea pig fissue cage model. RELEVANCE (See instructions):

葡萄球菌是我们社会的重大负担，导致大量发病率，死亡率和成本增加在医疗保健中。增加这种疾病的负担是他们在生物材料中形成生物膜的能力对Anfibiofics的耐受性和免疫系统的作用。进一步研究发展和葡萄球菌生物膜的成熟可能会导致新的治疗方法，从而导致它们的破坏。已知葡萄球菌生物膜表现出包含多种生理状态的空间异质性包括有氧和厌氧区。这些生理状态的维持至关重要成熟生物膜的发展。假设精氨酸的分解代谢对于发展至关重要以及金黄色葡萄球菌和表皮链球菌生物膜内厌氧区的成熟。实际上，金黄色葡萄球菌和表皮链球菌的几个背景都包含两个精氨酸的完整副本 Deiminase（ADI）操纵子，其中一个是在致病岛上获得的。 ADI操纵子合成分解精氨酸在ATP和氨中的蛋白质。在Biofllm的某些微观中环境，所得的ATP可用于代谢目的，而氨可以用于 pH稳态。研究表明，在生物膜发育期间诱导精氨酸代谢和获得的（即从致病性岛）ADI操纵子作为生物膜最活跃成熟。首先探索ARCR的调节作用，将研究精氨酸代谢的重要性在生物膜生长期间，已知的ADI表达调节剂。假设最大诱导获得的ADI操纵子发生在生物膜生长期间，在这些条件下的诱导是弧度其次，通过使用荧光基因融合，我们将检查时间和空间表皮链球菌和金黄色葡萄球菌中ADI基因表达的模式，并将这些数据与生物膜的已知厌氧和有氧区域。 Lasfiy，通过小鼠异物感染模型，与野生型S.金黄色葡萄球菌和表皮链球菌相比，ADI突变体的相对毒力可以确定。 ADI突变体对脂肪生物的可疑性将在豚鼠fissue笼模型中进行测试。相关性（请参阅说明）：