S. mutans: Its mutacin Antibiotic

S. mutans：其突变蛋白抗生素

• 批准号: 6753428
• 负责人: FENGXIA QI
• 金额: $ 3.47万
• 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/6753428
• 关键词: S.; mutans; Its; mutacin; Antibiotic

DESCRIPTION (provided by applicant): Streptococcus mutans is the major etiologic agent responsible for Dental caries, the most prevalent disease in 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. Production of mutacin is under the control of the same regulatory networks involved with stress response, quorum sensing, competence development and biofilm formation. Thus the production of mutacin may play a double role: it may give the producer strain a competitive edge in gaining dominance in the Dental plaque, leading to Dental caries, at the same time, 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 production with the following approaches: Specific Aim 1, to elucidate the mechanism of regulation for mutacin production. Specific Aim 2, to develop mutacin into a future antimicrobial drug. The proposed research will have a significant impact on two fronts. The first front is the alarming surge in resistance to the existing battery of antibiotics among emerging and existing bacterial pathogens, and the increasing threat of bio-terrorist attack using genetically engineered anthrax 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 in S. mutans during stress response and biofilm formation. This knowledge will help design effective measures to control the growth and virulence of S. mutans in the Dental plaque.

描述(申请人提供)：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常见的疾病。大多数变形链球菌的临床分离株都能产生称为变形链球菌素的抗菌肽。Mutacins对广泛的革兰氏阳性细菌具有活性，包括病原体和口腔共生菌。突变蛋白的产生受到相同的调控网络的控制，这些网络涉及胁迫反应、群体感应、能力发展和生物膜形成。因此，突变蛋白的产生可能起到双重作用：它可以使生产者菌株在牙菌斑中获得优势，从而导致龋齿；同时，它可以保护人类宿主免受革兰氏阳性细菌的感染。本研究旨在从遗传学、生物化学和生物学等方面研究变异素的产生，具体方法如下：1.阐明变异素产生的调控机制。具体目标2，将突变菌素开发成未来的抗菌药物。拟议的研究将在两个方面产生重大影响。第一个方面是新出现的和现有的细菌病原体对现有抗生素组的抗药性惊人地激增，以及使用对所有现有抗生素具有抗药性的基因工程炭疽病原体发动生物恐怖袭击的威胁越来越大。这些威胁强调了寻找尚未产生抗药性的非常规抗生素的重要性和紧迫性。第二个方面是了解变形链球菌在应激反应和生物膜形成过程中的基因调控机制。这些知识将有助于设计有效的措施来控制牙菌斑中变形链球菌的生长和毒力。