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（改编自调查员的摘要）：局部少年 牙周炎（LJP）是细菌积聚在 口腔中的连接上皮。它是在中间发现的 最后十年的肌动杆菌肌动症是主要的病因 LJP的代理商，最近，作为负责的微生物之一 成人牙周炎。牙周炎是最普遍的慢性炎症 人类的疾病，这是导致牙齿脱落的主要原因。很明显 这种牙齿病原体在传染过程中积极生长，并持续存在 这取决于这种微生物获得生长的能力 诸如铁等营养。脊椎动物宿主的铁预扣是有效的 针对细菌感染的机制，因此细菌必须表达 有效的运输系统以获取这种必不可少的养分以繁殖 在感染期间。有迹象表明A.放线菌没有 分泌铁载体化合物，它可能通过 周质结合蛋白依赖性转运系统。但是，基因和 这些过程中涉及的细菌产品及其在毒力中的作用 仍然有待表征。因此，这是长期目标 应用是A.的机制的表征。 放线菌的人用来获取铁及其参与 少年和成人牙周炎的发病机理。在此提案中， 首席研究者通过多种方法来解决这些目标， 结合经典和分子细菌遗传学的方法与 分子生物学技术旨在检查差异基因表达。 第一个特定目的涉及详细的遗传和分子 表征两个潜在的铁周质传输系统，而 第二个特定目的重点是分析这些系统的表达 在细菌培养基和组织培养中培养的细菌细胞中 包含人口腔上皮细胞的单层的烧瓶。第三个特定 目的建议确定这些潜在铁运输系统在 通过创建和 测试异源突变体。这些拟议的研究涉及一个重要的 A。 放线症。此外，这些研究将导致更好 理解主机与这之间互动的性质 在定植和口腔组织入侵期间的病原体。

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