IRON ACQUISITION BY STAPHYLOCOCCI

葡萄球菌的生长可被转铁蛋白抑制， 铁结合蛋白 据推测，人类感染期间的生长也是 依赖于葡萄球菌从宿主获得铁的能力。 尽管之前的研究已经研究了 革兰氏阴性菌获得铁，很少有工作已经做， 阐明革兰氏阳性菌的作用机制。 几十年来， 金黄色葡萄球菌一直是一个重要的原因， 医院获得性血流感染 最近葡萄球菌 表皮炎已成为医院感染的最常见原因之一， 血液感染 然而，人们对这种机制知之甚少， 葡萄球菌与脱铁转铁蛋白竞争。 该建议的长远目标是制定一个全面的 葡萄球菌获得铁的机制图。 的测定 （55）从各种底物（包括脱铁转铁蛋白）吸收的Fe将是 用于确定哪些作为铁源。 其他国家使用的机制 将对细菌进行评估，以确定它们是否在铁中起作用。 由葡萄球菌获得：细菌铁螯合物（铁载体）， 细菌还原酶、细菌或宿主衍生的有机酸。 机制 使用S。金葡菌将被比较和对比与那些使用的 毒性较小的葡萄球菌。 临床研究者奖将使主要研究者（PI） 解决关于葡萄球菌性脑膜炎发病机制的关键问题， 感染. 这些数据将提供重要的见解， 由S.金黄色葡萄球菌和毒性较小的葡萄球菌 物种 目的是开发铁的抗菌活性 预防和治疗贫困的新方法 葡萄球菌感染 此外，PI将获得经验 这对她未来作为独立调查员的职业生涯至关重要。

The growth of staphylococci can be inhibited by aportransferrin, the serum iron-binding protein. Presumably, growth during human infections is also dependent on the ability of staphylococci to acquire iron from the host. Although previous research has examined the mechanisms by which gram-negative organisms acquire iron, little work has been done to elucidate the mechanisms used by gram-positive organisms. For decades, Staphylococcus aureus has been an important cause of community- and hospital-acquired bloodstream infections. Recently Staphylococcus epidermidis has become one of the most common causes of nosocomial bloodstream infections. Yet little is known about the mechanisms by which staphylococci compete with apotransferrin. The long-term objective of the proposal is to develop a comprehensive picture of the mechanisms by which staphylococci acquire iron. Assays of (55)Fe uptake from various substrates, including apotransferrin, will be used to determine which serve as iron sources. Mechanisms used by other bacteria will be evaluated to determine whether they have a role in iron acquisition by staphylococci: bacterial iron chelators (siderophores), bacterial reductases, bacteria- or host-derived organic acids. Mechanisms used by S. aureus will be compared and contrasted with those used by the less virulent staphylococcal species. The Clinical Investigator Award will enable the Principal Investigator (PI) to address critical questions regarding the pathogenesis of staphylococcal infections. The data will give important insights into the differences between infections caused by S. aureus and by less virulent staphylococcal species. The goal is to develop the antibacterial activity of iron deprivation into new approaches for the prevention and treatment of staphylococcal infections. In addition, the PI will gain experience essential for her future career as an independent investigator.