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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 被称为化脓性链球菌和金黄色葡萄球菌的细菌是引起多种疾病的重要人类病原体，包括链球菌性咽喉炎、中毒性休克综合征和/或皮肤感染。 这些细菌需要铁来生长。 然而，游离铁在人体组织中非常稀缺，细菌已经开发了几种方法来获得其生长所需的铁。 哺乳动物体内的铁主要是血红素，存在于某些蛋白质中。 例如，人体中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，细菌已经开发了从宿主蛋白质中获取血红素并将其内化的方法，血红素被降解以提供细菌细胞所需的铁。 在化脓性链球菌和金黄色葡萄球菌中血红素的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还不清楚。 研究了化脓性链球菌和金黄色葡萄球菌表面蛋白在血红素获取过程中的作用。 化脓性链球菌的表面蛋白Shr结合血红素，另一种表面蛋白Shp将血红素从Shr传递到跨膜转运蛋白。 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，这些表面蛋白质中继血红素从宿主蛋白质的转运随后的内化。 这些结果大大提高了我们的理解，血红素收购化脓性链球菌和金黄色葡萄球菌的机制，并可能作为一个通用的模型血红素收购在许多其他革兰氏阳性病原体。 了解这些细菌如何利用血红素在人体内生存，可能会为如何阻止血红素运输提供线索，以开发新的治疗方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.