Effect of Arginine Metabolism on Biofilm Formation in the Staphyloccoci

葡萄球菌是我们社会的主要负担，导致显着的发病率、死亡率和成本增加 在医疗保健方面。增加这种疾病负担的是它们在生物材料上形成生物膜的能力 增加对抗生素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的出现，从而破坏其生物膜。 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 包括有氧区和无氧区。维持这些生理状态对于 形成成熟的生物膜。据推测，精氨酸分解代谢对于发育至关重要 金黄色葡萄球菌和表皮葡萄球菌生物膜内厌氧区域的成熟。事实上， 金黄色葡萄球菌和表皮葡萄球菌的几个背景都含有两个完整的精氨酸副本 脱亚胺酶（ADI）操纵子，其中之一是在致病岛上获得的。 ADI操纵子合成 分解代谢精氨酸并重新磺化为 ATP 和氨的蛋白质。在生物膜的某些微生态位内 环境中，产生的 ATP 可用于代谢目的，而氨可用于 pH 稳态。研究表明精氨酸代谢是在生物膜发育过程中被诱导的 获得的（即来自致病岛的）ADI操纵子与生物膜一样具有最强的转录活性 成熟。将通过首先探索ArcR的调节作用来研究精氨酸代谢的重要性， 生物膜生长过程中 ADI 表达的已知调节因子。据推测，最大诱导 获得性 ADI 操纵子发生在生物膜生长过程中，并且在这些条件下进行诱导是 ArcR- 其次，通过使用荧光基因融合，我们将检查时间和空间 表皮葡萄球菌和金黄色葡萄球菌生物膜内的 ADI 基因表达模式，并将这些数据与 生物膜的已知厌氧和需氧区域。 Lasfiy通过小鼠异物感染模型， 与野生型金黄色葡萄球菌和表皮葡萄球菌相比，ADI突变体的相对毒力待确定。 ADI 突变体对抗生素的敏感性将在豚鼠组织笼模型中进行测试。 相关性（参见说明）：

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):