Leukotoxin production by A. actinomycetemcomitans

A. actinomycetemcomitans 产生白细胞毒素

基本信息

批准号：
7434168
负责人：
SCOTT C KACHLANY
金额：
$ 1.25万
依托单位：
UNIV OF MED/DENT OF NJ-NJ DENTAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7434168
关键词：
Actinobacillus actinomycetemcomitans Adenylate Cyclase Adolescent Affect Amino Acids Anabolism Bacteria Biochemical Biochemical Genetics Biological Assay Cells Class Collaborations Condition Crystallization DNA Sequence Analysis Disease Ensure Failure Frequencies Gene Proteins Genes Genetic Goals Heart Valve Diseases Hemolysin Human Immune response Immunoprecipitation Incidence Infective endocarditis Laboratories Lead Leukocytes Light Localized Methods Minority Molecular Molecular Structure Mouth Diseases Pathogenesis Periodontitis Pertussis Play Population Group Production Proteins Regulation Reporter Genes Resolution Role Structure Techniques Testing Therapeutic Agents Tissues Tooth Loss Toxin Vibrio cholerae Virulence Factors Work design factor A gene function intracellular protein transport leukotoxin mutant pathogen prevent protein function protein localization location research study success three dimensional structure tool yeast two hybrid system

项目摘要

Actinobacillus actinomycetemcomitans is a bacterium that is the etiologic agent for localized aggressive periodontitis (LAP). LAP is a destructive and aggressive disease of the oral cavity that affects adolescents. The incidence of LAP varies among population groups, but afflicts minorities and the underprivileged at a higher frequency. Failure to treat LAP results in the loss of teeth and other health-related problems. In addition, A. actinomycetemcomitans is part of the HACEK group of bacteria that causes infective endocarditis, a disease of heart valves and tissue. A. actinomycetemcomitans secretes a protein toxin known as leukotoxin. Leukotoxin destroys leukocytes of humans, and likely plays a significant role in the pathogenesis of A. actinomycetemcomitans by helping the bacterium evade the immune response. Leukotoxin is an RTX (repeats in toxin) toxin that includes other important toxins such as E. coil alpha-hemolysin, M. haemolytica leukotoxin, B. pertussis adenylate cyclase, and V. cholerae RTX toxin. To date, little is known about how A. actinomycetemcomitans leukotoxin is produced, activated, and secreted from bacterial cells. In addition, none of the RTX toxins have been crystallized to have their three-dimensional structures solved. Proposed here are experiments that will (1) identify the genes that are required for production of active leukotoxin, (2) study the genes and proteins using genetic and biochemical approaches, and (3) grow crystals of leukotoxin and solve its three-dimensional structure at the atomic level. We expect this work to lead to a better understanding of leukotoxin production and how the toxin contributes to disease. The structural information gained through these experiments will shed more light on the mechanism of action of this important class of toxins. This new information may lead to the design of therapeutic agents that can disrupt leukotoxin activity and ultimately treat or prevent disease.

放线杆菌放线菌Cetemcitans是一种细菌，是局部攻击性的病因学剂牙周炎（圈）。膝盖是影响青少年的口腔破坏性和侵略性疾病。人口群体之间的膝上发生率有所不同，但遭受了少数群体和贫民窟的困扰较高的频率。无法治疗膝盖会导致牙齿丧失和其他与健康有关的问题。在另外，A。放线菌CeTemcomitans是导致感染性的细菌组的一部分心内膜炎，一种心脏瓣膜和组织疾病。 A.放线菌co虫分泌一种称为白细胞毒素的蛋白质毒素。白细胞毒素破坏人类的白细胞，可能在曲霉的曲霉曲霉的发病机理中起重要作用。帮助细菌逃避免疫反应。白细胞毒素是RTX（在毒素中重复）毒素包括其他重要的毒素，例如E. coil alpha-Hemolysin，M。hemolytica leukotoxin，b。pltussis 腺苷酸环化酶和V.霍乱RTX毒素。迄今为止，对A. actinomycetemcomitans的了解知之甚少白细胞毒素是从细菌细胞中产生，激活和分泌的。另外，RTX毒素没有结晶以解决其三维结构。此处提出的实验将（1）确定生产活性所需的基因白细胞毒素（2）使用遗传和生化方法研究基因和蛋白质，（3）生长白细胞毒素的晶体并在原子水平上解决其三维结构。我们希望这项工作能够可以更好地了解白细胞毒素的产生以及毒素如何对疾病有效。这通过这些实验获得的结构信息将更多地了解这类重要的毒素类。这些新信息可能会导致设计的治疗剂破坏白细胞毒素活性，最终治疗或预防疾病。