S. mutans: Its mutacin Antibiotic

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普遍的疾病。大多数临床分离的变形链球菌产生抗微生物肽，称为诱变素。诱变素对广泛的革兰氏阳性细菌有活性，包括病原体和口腔共生菌。诱变素的产生受到与应激反应、群体感应、能力发展和生物膜形成相同的调控网络的控制。因此，突变素的产生可能起到双重作用：它可能使产生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。本研究拟从以下几个方面对诱变霉素产生的遗传、生化和生物学方面进行研究：具体目的1，阐明诱变霉素产生的调控机制。具体目标2，将突变素发展成为未来的抗菌药物。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的耐药性惊人地激增，以及利用对所有现有抗生素具有耐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。第二个方面是了解变异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变形链球菌在牙菌斑中的生长和毒力。

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.