Prevotella intermedia: Iron and Virulence

描述（由申请人提供）：中普雷沃氏菌与口腔（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。建立感染的一个重要步骤是病原体在其宿主内繁殖的能力。这种特性在很大程度上受铁等营养物质的可用性的影响。血红蛋白已被证明是这些细菌不可缺少的营养物质。它是铁和原卟啉IX的来源。因此，我们将从研究血红素获得的分子机制开始研究这种细菌的毒力特征。首先，我们将确定与色素沉着位点有关的基因。在口腔革兰氏阴性菌中，黑色色素沉着是由于血红蛋白在细胞表面的积累。我们假设有几个基因编码参与血红蛋白整合的蛋白质。此外，我们假设参与血红蛋白/铁转运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节基因产物的最佳方法。使用这种方法，我们打算鉴定受铁耗尽影响的蛋白质。我们的研究结果将有助于确定铁摄取机制，这可能是未来设计中间芽孢杆菌抗菌剂的目标。由于中间芽孢杆菌对许多抗生素具有耐药性，因此需要对这种细菌采取其他预防措施。

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.