IRON UPTAKE IN ACTINOBACILLUS ACTINOMYCETEMCOMITANS

伴放线放线杆菌中的铁吸收

• 批准号: 6757187
• 负责人: Luis A Actis
• 金额: $ 12.6万
• 依托单位: MIAMI UNIVERSITY OXFORD
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6757187
• 关键词: Actinobacillus actinomycetemcomitans; SDS polyacrylamide gel electrophoresis; bacteria infection mechanism; bacterial genetics; bacterial proteins; clone cells; epithelium; gene expression; genetic library; genetic mapping; genetic promoter element; iron metabolism; membrane transport proteins; mutant; northern blottings; nucleic acid sequence; operon; oral bacteria; pathologic process; periodontitis; polymerase chain reaction; siderophores; site directed mutagenesis; southern blotting; virulence; western blottings

DESCRIPTION (adapted from the Investigator's abstract): Localized juvenile periodontitis (LJP) is the disease that occurs when bacteria accumulate on the junctional epithelium in the oral cavity. It was found in the middle of the last decade that Actinobacillus actinomycetemcomitans is the major causative agent of LJP and, more recently, as one of the microorganisms responsible for adult periodontitis. Periodontitis is the most prevalent chronic inflammatory diseases in humans, and it is major cause of tooth loss. It is evident that this dental pathogen grows actively and persists during the infectious process, which depends upon the ability of this microorganism to obtain growth-essential nutrients such as iron. Iron withholding by vertebrate hosts is an efficient mechanism against bacterial infections, and, thus bacteria must express efficient transport systems to acquire this essential nutrient to multiply during infection. There are indications that A. actinomycetemcomitans does not secrete siderophore compounds and it may acquire iron through periplasmic-binding protein-dependent transport systems. However, the genes and bacterial products involved in these processes and their role in virulence remain to be characterized. Therefore, the long-term objective of this application is the characterization of the mechanisms that A. actinomycetemcomitans uses to acquire iron and their participation in the pathogenesis of juvenile and adult periodontitis. In this proposal, the Principal Investigator addresses these goals through several approaches, combining methods used in classical and molecular bacterial genetics with molecular biology techniques designed to examine differential gene expression. The first specific aim involves a detailed genetic and molecular characterization of two potential iron periplasmic-transport systems, while the second specific aim focuses on the analysis of the expression of these systems in bacterial cells cultured in bacteriological media and in tissue culture flasks containing monolayers of human oral epithelial cells. The third specific aim proposes to determine the role of these potential iron transport systems in iron acquisition and the virulence of A. actinomycetemcomitans by creating and testing isogenic mutants. These proposed studies address an important and largely unexplored aspect of the pathogenesis caused by A. actinomycetemcomitans. Furthermore, these studies will lead to a better understanding of the nature of the interactions between the host and this pathogen during colonization and invasion of oral tissues.

描述(改编自调查人员摘要)：本地化青少年 牙周炎(LJP)是当细菌在牙周上堆积时发生的疾病 口腔中的连接上皮。它是在市中心被发现的 近十年来，伴生放线杆菌是主要原因 LJP的代理人，最近作为一种负责 成人牙周炎。牙周炎是最常见的慢性炎症性疾病 是人类的主要疾病，也是牙齿脱落的主要原因。很明显， 这种牙科病原体在感染过程中活跃生长并持续存在， 这取决于这种微生物获得生长所必需的能力 营养物质，如铁。脊椎动物宿主扣留铁是一种有效的 抗细菌感染的机制，因此细菌必须表达 高效的运输系统，以获得这种繁殖所必需的营养 在感染期间。有迹象表明，伴生放线菌不会 分泌铁载体化合物，它可能通过 依赖于周质结合蛋白的运输系统。然而，基因和 参与这些过程的细菌产物及其在毒力中的作用 仍有待定性。因此，这一行动的长期目标是 应用是对A。 伴生放线菌用来获取铁及其在体内的参与 青少年和成人牙周炎的发病机制。在这项提案中， 首席调查员通过几种方法解决这些目标， 将经典和分子细菌遗传学中使用的方法与 用来检测差异基因表达的分子生物学技术。 第一个具体目标涉及详细的遗传和分子 两个潜在的铁周质运输系统的特征，而 第二个具体目的是分析这些制度的表现形式 在细菌培养液和组织培养中培养的细菌细胞中 装有人类口腔上皮细胞单层的烧瓶。第三个具体问题 AIM建议确定这些潜在的铁运输系统在 铁的获取和伴生放线菌通过产生和产生的毒力 测试同基因突变体。这些拟议的研究涉及一个重要的和 在很大程度上尚未被探索的致病机制方面由A. 伴生放线菌。此外，这些研究将导致更好的 理解宿主与此之间的相互作用的性质 口腔组织定植和入侵过程中的病原体。

项目成果

Evaluation of different iron sources and their influence in biofilm formation by the dental pathogen Actinobacillus actinomycetemcomitans.

评估不同铁源及其对牙科病原体伴放线放线杆菌生物膜形成的影响。

• DOI: 10.1099/jmm.0.46844-0
• 发表时间: 2007
• 期刊: Journal of medical microbiology
• 影响因子: 3
• 作者: Rhodes,EricR;Shoemaker,ChristopherJ;Menke,SharonM;Edelmann,RichardE;Actis,LuisA
• 通讯作者: Actis,LuisA