Prevotella intermedia: Iron and Virulence

描述(申请人提供)：中间普雷沃特氏菌与口腔(牙周病和牙髓感染)和口腔外感染有关。尽管这种微生物与疾病有关，但人们对其毒力的遗传或生化基础知之甚少。确定感染的一个重要步骤是病原体在其宿主内繁殖的能力。这一特性很大程度上受到铁等营养素可用性的影响。氯化血红素已被证明是这些细菌不可或缺的营养物质。它是铁和原卟啉IX的来源。因此，我们将从研究氯化血红素获得的分子机制入手，开始研究该细菌的毒力特征。首先，我们将确定与色素沉着基因相关的基因。在口腔革兰氏阴性细菌中，黑色色素是由于细胞表面积累的氯化血红素造成的。我们假设有几个基因编码参与整合氯化血红素的蛋白质。此外，我们假设参与氯化血红素/铁运输的基因是由铁协调调节的。蛋白质组学是快速鉴定大量差异调控基因产物的最佳方法。使用这种方法，我们打算识别受铁缺乏影响的蛋白质。我们的研究结果将有助于确定铁摄取机制，这些机制可能在未来设计中间假单胞菌的抗菌剂时充当靶标。由于中间假单胞菌对许多抗生素具有抗药性，因此需要对这种细菌采取替代的预防措施。

DESCRIPTION (provided by applicant): Prevotella intermedia is associated with both oral (periodontal disease and endodontic infections) and extraoral infections. Despite this organism's association with disease little is known about the genetic or biochemical basis of its virulence. An essential step in establishment of an infection is the ability of a pathogen to multiply within its host. This property is greatly influenced by availability of nutrients such as iron. Hemin has been shown to be an indispensable nutrient for these bacteria. It serves as a source of iron and protoporphyrin IX. Thus, we will start our study of the virulence features of this bacterium by investigating the molecular mechanisms of hemin acquisition. First, we shall identify the genes involved in the pigmentation locus. In oral gram-negative bacteria, black pigmentation results from accumulation of hemin on the cell surface. We hypothesize that there are several genes coding for the proteins participating in the integration of hemin. Furthermore, we hypothesize that the genes involved in hemin/iron transport are coordinately regulated by iron. Proteomics is the best approach to rapidly identify large numbers of differentially regulated gene products. Using this approach we intend to identify proteins affected by iron depletion. The results of our study will help define iron uptake mechanisms that may serve as targets in the future design of antibacterial agents for P. intermedia. Since P. intermedia is resistant to many antibiotics alternative methods of preventive measures are needed for this bacterium.