S. mutans: Its mutacin Antibiotic

描述：变形链球菌是龋齿的主要病原，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。因此，变形链球菌产生的突变素可能起双重作用：它为产生突变的菌株提供了在牙菌斑中获得支配地位的竞争优势，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感染。本研究拟从以下几个方面研究诱变霉素生物发生和调控的遗传、生化和生物学方面：目的1，表征诱变霉素基因调控的反式作用因子。目的2，表征调节诱变素基因表达的顺式作用因子。目的3：通过基因工程确定诱变素分子的结构/功能，改善诱变素的性能。目的4：促进诱变素生物合成，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，以及利用基因工程病原体对所有现有抗生素产生耐药性的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产生诱变素的基因调控机制。这一知识将有助于设计有效的控制措施，以抑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.