Heme and hemoglobin utilization by Mycobacterium tuberculosis

项目摘要-结核分枝杆菌对血红素和血红蛋白的利用 结核分枝杆菌(Mtb)是最重要的细菌病原体之一。铁是 对结核分枝杆菌的生长是必不可少的，但铁有效地隔离在人类宿主中。血红蛋白是 到目前为止，人体内最普遍的铁源，通常是细菌偏好的铁源 病原体。最近，我们发现了一种蛋白质，它们是一种前所未有的 结核分枝杆菌中的血红素和血红蛋白利用系统。有趣的是，这些新的血红素结合 血红蛋白的利用也需要蛋白质，这表明血红素是从 血红蛋白通过一种未知的机制在结核杆菌细胞表面，然后转移到 血红素摄取系统。本建议旨在阐明血红素和血红素的分子机制。 结核分枝杆菌对血红蛋白的利用。该项目将使我们更好地了解MTB如何获得 在感染期间获得铁的途径。为了实现这些目标，我们采用了最先进的基因， 生化、生物物理和结构方法。

Project Summary - Heme and hemoglobin utilization by Mycobacterium tuberculosis Mycobacterium tuberculosis (Mtb) is of one of the most important bacterial pathogens. Iron is essential for growth of Mtb, but iron is efficiently sequestered in the human host. Hemoglobin is by far the most prevalent iron source in the human body and is often preferred by bacterial pathogens. Recently, we identified proteins that are essential components of an unprecedented heme and hemoglobin utilization system in Mtb. Interestingly, these novel heme-binding proteins are also required for utilization of hemoglobin indicating that heme is released from hemoglobin at the cell surface of Mtb by an unknown mechanism and then transferred to the heme uptake system. This proposal aims to elucidate the molecular mechanisms of heme and hemoglobin utilization by Mtb. This project will lead to a better understanding of how Mtb gains access to iron during infection. To achieve these goals we employ state-of-the-art genetic, biochemical, biophysical and structural methods.