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Prevotella intermedia: Iron and Virulence

中间普雷沃氏菌：铁和毒力

基本信息

批准号：
6760218
负责人：
Janina P Lewis
金额：
$ 7.5万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-01 至 2006-04-30
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：中间普雷沃菌与口腔（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，但对其毒性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。这种特性受到营养素如铁的可用性的极大影响。氯化血红素已被证明是这些细菌不可或缺的营养素。它是铁和原卟啉IX的来源。因此，我们将开始我们的研究，这种细菌的毒力特点，调查氯化血红素收购的分子机制。首先，我们将确定参与色素沉着位点的基因。在口腔革兰氏阴性细菌中，黑色色素沉着是由于氯化血红素在细胞表面的积累。我们推测，有几个基因编码的蛋白质参与整合氯化血红素。此外，我们推测，参与氯化血红素/铁转运的基因是由铁协调调节。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，我们打算确定受铁消耗影响的蛋白质。我们的研究结果将有助于确定铁的吸收机制，可能作为目标，在未来的抗菌剂设计的中间型青霉菌。由于P. intermedia对许多抗生素具有耐药性，因此需要针对该细菌的预防措施的替代方法。