S. mutans: Its mutacin Antibiotic

描述：变形链球菌是导致龋齿的主要病原体，龋病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。因此，变形链球菌产生的突变蛋白可能起到双重作用：它为产生突变的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的感染。本研究旨在从遗传学、生物化学和生物学的角度研究突变蛋白的生物发生和调控。目的1、研究突变蛋白基因调控的反式作用因子。目的2、研究调控突变素基因表达的顺式作用因子。目的3、利用基因工程技术确定变构体分子的结构和功能，改善变构体的性质。目的4、提高变形菌素的生物合成能力，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的耐药性惊人地激增，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产生突变蛋白的基因调控机制。这些知识将有助于设计有效的控制措施，以遏制变形链球菌在牙菌斑中的生长和毒力。

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.