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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 化脓性链球菌和金黄色葡萄球菌是人类重要的病原体，可引起多种疾病，包括链球菌咽喉、中毒性休克综合征和/或皮肤感染。这些细菌需要铁才能生长。然而，人体组织中的游离铁相当稀缺，细菌已经开发出几种方法来获取它们生长所需的铁。哺乳动物体内的铁主要是血红素，它存在于一些蛋白质中。例如，人类中最常见的含有血红素的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中获取血红素并将其内化的方法，这些血红素被降解，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捕获机制由表面蛋白和跨膜转运蛋白组成。然而，血红素获得过程的具体途径和机制还不是很清楚。研究了化脓性链球菌和金黄色葡萄球菌表面蛋白在这两种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传递到跨膜转运体。研究还表明，金黄色葡萄球菌的表面蛋白ISDA可以直接、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体，以便随后内化。这些结果极大地加深了我们对化脓性链球菌和金黄色葡萄球菌中获得血红素的机制的理解，并可作为许多其他革兰氏阳性病原菌获得血红素的通用模型。了解这些细菌是如何利用血红素在人类体内生存的，可能会为如何阻止血红素的运输提供线索，从而开发新的疗法来对抗这些有害的病原体。

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.