Effect of Arginine Metabolism on Biofilm Formation in the Staphyloccoci

葡萄球菌是我们社会的主要负担，导致严重的发病率、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，结果是 增强对抗菌素的耐受性和免疫系统的作用。关于发展的进一步研究和 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。 葡萄球菌生物膜表现出包含几种生理状态的空间异质性。 包括好氧区和厌氧区。这些生理状态的维持对于 开发成熟的生物膜。推测精氨酸分解代谢对发育是至关重要的。 以及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种背景都含有两个完整的精氨酸拷贝。 脱亚胺酶(ADI)操纵子，其中一个是在致病岛上获得的。ADI操纵子合成 分解精氨酸的蛋白质，生成三磷酸腺苷和氨。在生物膜的某些微米级内 在环境中，生成的三磷酸腺苷可用于代谢目的，而氨可用于 PH动态平衡。研究表明，精氨酸代谢是在生物膜发育和 获得性(即来自致病岛)ADI操纵子作为生物膜在转录上最活跃 成熟了。精氨酸代谢的重要性将首先通过探索ArcR的调节作用来研究， 一种已知的ADI表达调节剂，在生物膜生长过程中。它假设最大诱发率是 获得性ADI操纵子发生在生物膜生长过程中，在这些条件下诱导的是ArcR- 其次，通过使用荧光基因融合，我们将检查颞骨和枢椎 表皮葡萄球菌和金黄色葡萄球菌生物膜中ADI基因的表达模式 已知的生物膜厌氧和需氧区域。Lasfiy，通过小鼠异物感染模型， 测定ADI突变株与野生型金黄色葡萄球菌和表皮葡萄球菌的相对毒力。 ADI突变体对抗菌素的敏感性将在豚鼠养殖场模型中进行测试。 相关性(请参阅说明)：

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):