MT VET COBRE PROJECT 2: METAL UPTAKE AND REGULATION IN STREPTOCOCCUS PYOGENES

MT VET COBRE 项目 2：化脓性链球菌的金属吸收和调节

• 批准号: 7721026
• 负责人: BENFANG LEI
• 金额: $ 17.99万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721026
• 关键词: Bacteria; Binding; Cells; Computer Retrieval of Information on Scientific Projects Database; Disease; Erythrocytes; Funding; Grant; Growth; Heme; Hemoglobin; Human; Infectious Skin Diseases; Institution; Iron; Mammals; Membrane Proteins; Metals; Modeling; Pathway interactions; Pharyngeal structure; Process; Proteins; Regulation; Research; Research Personnel; Resources; Role; Source; Staphylococcus aureus; Streptococcus pyogenes; Toxic Shock Syndrome; United States National Institutes of Health; human tissue; novel therapeutics; pathogen; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The bacteria known as Streptococcus pyogenes and Staphylococcus aureus are important human pathogens that cause a variety of diseases, including strep throat, toxic shock syndrome, and/or skin infection. These bacteria require iron for growth. However, free iron is quite scarce in human tissues, and bacteria have developed several approaches for acquiring the iron needed for their growth. The majority of iron in mammals is heme, which is present in some proteins. For example, one of the most common heme-containing proteins in humans is hemoglobin from red blood cells. To obtain iron, bacteria have developed approaches for acquiring heme from host proteins and internalizing it, which is degraded to provide bacterial cells with the needed iron. The heme acquisition machineries in Streptococcus pyogenes and Staphylococcus aureus consist of surface proteins and a transmembrane transporter. However, the specific pathway and mechanism of the heme acquisition process are not well understood. The roles of the surface proteins of Streptococcus pyogenes and Staphylococcus aureus in the heme acquisition process by these bacteria have been studied. The surface protein Shr of Streptococcus pyogenes binds heme, and the other surface protein Shp relays heme from Shr to the transmembrane transporter. It also has been demonstrated that the surface protein IsdA of Staphylococcus aureus directly and rapidly transfers its heme to the other surface protein IsdC. These studies suggest that these surface proteins relay heme from host proteins to the transporter for subsequent internalization. These results greatly enhance our understanding of the mechanisms of heme acquisition in Streptococcus pyogenes and Staphylococcus aureus and may serve as a general model for heme acquisition in many other Gram-positive pathogens. Understanding of how these bacteria utilize heme to survive in humans may provide clues on how to block the heme transport for developing new therapeutics to combat these harmful pathogens.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 化脓性链球菌和金黄色葡萄球菌是重要的人类病原体，可引起多种疾病，包括链球菌性咽喉炎、中毒性休克综合征和/或皮肤感染。 这些细菌的生长需要铁。 然而，人体组织中的游离铁相当稀缺，细菌已经开发出多种方法来获取其生长所需的铁。 哺乳动物中的大部分铁是血红素，它存在于一些蛋白质中。 例如，人类最常见的含血红素蛋白质之一是来自红细胞的血红蛋白。 为了获得铁，细菌已经开发出从宿主蛋白质中获取血红素并将其内在化的方法，血红素被降解以为细菌细胞提供所需的铁。 化脓性链球菌和金黄色葡萄球菌的血红素获取机制由表面蛋白和跨膜转运蛋白组成。 然而，血红素获取过程的具体途径和机制尚不清楚。 已经研究了化脓性链球菌和金黄色葡萄球菌的表面蛋白在这些细菌获取血红素过程中的作用。 化脓性链球菌的表面蛋白 Shr 与血红素结合，另一种表面蛋白 Shp 将血红素从 Shr 传递到跨膜转运蛋白。 还证明金黄色葡萄球菌的表面蛋白IsdA可以直接且快速地将其血红素转移到另一种表面蛋白IsdC上。 这些研究表明这些表面蛋白将血红素从宿主蛋白传递到转运蛋白以进行随后的内化。 这些结果极大地增强了我们对化脓性链球菌和金黄色葡萄球菌血红素获取机制的理解，并可作为许多其他革兰氏阳性病原体中血红素获取的通用模型。 了解这些细菌如何利用血红素在人体中生存，可能会为如何阻止血红素运输提供线索，从而开发新的疗法来对抗这些有害病原体。