S. mutans: Its mutacin Antibiotic

描述（由申请人提供）：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普遍的疾病。大多数临床分离的S.变异体产生称为变异蛋白的抗微生物肽。突变素对广泛的革兰氏阳性菌具有活性，包括病原体和口腔病原体。突变蛋白的产生受到与应激反应、群体感应、感受态发育和生物膜形成有关的相同调节网络的控制。因此，变蛋白的产生可能发挥双重作用：它可能使生产菌株在牙菌斑中获得优势，从而导致龋齿，同时它可能保护人类宿主免受革兰氏阳性细菌感染。本研究的目的是通过以下方法研究突变蛋白产生的遗传、生物化学和生物学方面：具体目的1，阐明突变蛋白产生的调控机制。具体目标2：将变霉素开发成未来的抗微生物药物。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的抗药性惊人地激增，以及利用对所有现有抗生素都有抗药性的基因工程炭疽病原体进行生物恐怖袭击的威胁日益增加。这些威胁强调了寻找非传统抗生素的重要性和紧迫性，对这些抗生素尚未产生耐药性。第二个方面是了解S.在应激反应和生物膜形成过程中的变形杆菌。这些知识将有助于设计有效的措施来控制S.牙菌斑中的变异体

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.