Regulation of carbon metabolism in staphylococci: The impact of catabolite control protein A and related factors on pathogenicity of Staphylococcus aureus and Staphylococcus epidermidis

碳分解代谢影响因子已在许多细菌中被证明影响毒力和致病。我们最近在金黄色葡萄球菌中发现了分解代谢控制蛋白A(CCPA)，它被认为是革兰氏阳性菌碳分解代谢抑制(CCR)的主要调节因子。在第一个资助期，我们可以证明该调控因子的缺失影响了该病原菌的碳代谢、毒力决定簇的产生和传染性。该项目第二个资助期的目的现在是描述金黄色葡萄球菌中这种DNA结合蛋白的调控特征，它对糖尿病患者常见感染的影响，以及它在宿主体内的持久性作用。我们还将试图确定金黄色葡萄球菌在宿主内的早期适应过程中发生的转录变化，并计划进一步表征影响这种生物的调节因子的碳代谢，如CitR、HPR和Cody。这项拟议的工作将对金黄色葡萄球菌及其宿主在入侵和持续期间有效的代谢过程，以及将这种病原体的碳代谢和毒力联系在一起的调控电路产生详细的见解。

Carbon catabolism-affecting factors have been shown in many bacteria to influence virulence and pathogenesis. We recently identified the catabolite control protein A (CcpA) in Staphylococcus aureus, which is thought to be the major regulator of carbon catabolite repression (CCR) in Gram-positive bacteria. During the first funding period, we could show that the deletion of this regulator affected carbon metabolism, virulence determinant production, and infectivity of this pathogen. Aim of the second funding period of this project is now the characterization of the regulatory control of this DNA-binding protein in S. aureus, its impact on infections that are frequent in diabetic patients, and its role in persistence within its host. We will also try to identify the transcriptional changes that occur during the early adaptation processes of S. aureus within its host, and we are planning to characterize further carbon metabolism-affecting regulators of this organism, such as CitR, Hpr, and CodY. The proposed work will yield detailed insights into metabolic processes that are effective within S. aureus and its host during invasion and persistence, and into regulatory circuits that link carbon metabolism and virulence in this pathogen.