S. mutans: Its mutacin Antibiotic

S. mutans：其突变蛋白抗生素

• 批准号: 6984110
• 负责人: FENGXIA QI
• 金额: $ 25.93万
• 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 2006-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6984110
• 关键词: S.; mutans; Its; mutacin; Antibiotic

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：链球菌突变是负责龋齿的主要病因，这是发达国家和发展中国家最普遍的疾病。大多数突变链球菌的临床分离株产生称为植物蛋白的抗菌肽。植物素对包括病原体和口服分数在内的革兰氏阳性细菌的广泛范围很活跃。因此，S。utans产生的Mutacin可能会发挥双重作用：它在获得牙齿斑块中具有竞争优势的产生应变，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的影响。拟议的研究旨在研究使用以下方法来研究植物素生物发生和调节的遗传，生化和生物学方面：目标1，以表征Mutacin Gene调控的跨作用因子。目的2，以表征调节毒素基因表达的顺式作用因子。目标3，确定植物素分子的结构/功能，并通过基因工程改善植物素的特性。目标4，以增强毒素生物合成并改善发酵条件。拟议的研究将对两个方面产生重大影响。首先是通过新兴和现有病原体抵抗现有的抗生素电池的令人震惊的激增，以及使用对所有现有抗生素的基因工程病原体具有抗性的生物恐怖攻击威胁。这些威胁是寻找非常规抗生素的重要性和紧迫性，而抗生素尚未开发出来。第二个方面是了解链球菌中育毒素产生基因调节的机理。这些知识将有助于设计有效的控制措施，以遏制牙菌斑中突变体的生长和毒力。