S. mutans: Its mutacin Antibiotic

S. mutans：其突变蛋白抗生素

• 批准号: 6623730
• 负责人: FENGXIA QI
• 金额: $ 31.75万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-03 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6623730
• 关键词: antibiotics; bacterial genetics; dental caries; dental plaque; fermentation; gel mobility shift assay; gene expression; genetic regulation; high performance liquid chromatography; immunoprecipitation; northern blottings; operon; peptides; polymerase chain reaction; site directed mutagenesis; tissue /cell culture; western blottings

DESCRIPTION: Streptococcus mutans is the major etiologic agent responsible for Dental caries, the most prevalent disease in the developed and developing countries. Most clinical isolates of S. mutans produce antimicrobial peptides called mutacins. Mutacins are active against a wide spectrum of Gram-positive bacteria including pathogens and oral commensals. Thus, mutacin production by S. mutans may play a double role: it provides the producing strain with a competitive edge in gaining dominance in the Dental plaque, leading to Dental caries. On the other hand, it may protect the human host from Gram-positive bacterial infections. The proposed research Aims to study the genetic, biochemical and biological aspects of mutacin biogenesis and regulation with the following approaches: Aim 1, to characterize the trans-acting factors for mutacin gene regulation. Aim 2, to characterize the cis-acting factors that regulate mutacin gene expression. Aim 3, to determine the structure/function of the mutacin molecule and improve the properties of mutacins by genetic engineering. Aim 4, to enhance mutacin biosynthesis and improve fermentation conditions. The proposed research will have a significant impact on two fronts. The first is the alarming surge in resistance to the existing battery of antibiotics by emerging and existing pathogens, and the increasing threat of bioterrorist attack using genetically engineered pathogens resistant to all existing antibiotics. These threats underpin the importance and urgency of finding unconventional antibiotics, to which resistance has not been developed. The second front is understanding the mechanism of gene regulation for mutacin production in S. mutans. This knowledge will help design effective control measures to curb the growth and virulence of S. mutans in the Dental plaque.

描述：变形链球菌是导致龋齿的主要病原体，龋齿是发达国家和发展中国家最普遍的疾病。大多数变形链球菌的临床分离株产生称为变异蛋白的抗菌肽。突变蛋白对多种革兰氏阳性菌具有活性，包括病原体和口腔共生菌。因此，变形链球菌产生的突变蛋白可能发挥双重作用：它为生产菌株提供了在牙菌斑中获得优势的竞争优势，从而导致龋齿。另一方面，它可以保护人类宿主免受革兰氏阳性细菌感染。拟议的研究旨在通过以下方法研究突变蛋白生物合成和调控的遗传、生化和生物学方面： 目标 1，表征突变蛋白基因调控的反式作用因子。目标 2，表征调节突变蛋白基因表达的顺式作用因子。目标3，确定突变蛋白分子的结构/功能，并通过基因工程改善突变蛋白的特性。目标4，增强突变蛋白生物合成，改善发酵条件。拟议的研究将在两个方面产生重大影响。首先是新出现的和现有的病原体对现有抗生素电池的耐药性急剧增加，以及使用对所有现有抗生素具有耐药性的基因工程病原体进行生物恐怖袭击的威胁日益增加。这些威胁凸显了寻找尚未产生耐药性的非常规抗生素的重要性和紧迫性。第二个前沿是了解变形链球菌中突变蛋白产生的基因调控机制。这些知识将有助于设计有效的控制措施，以抑制牙菌斑中变形链球菌的生长和毒力。