S MUTANS--CHARACTERIZATION OF ITS MUTACIN ANTIBIOTIC

S mutans--其突变蛋白抗生素的表征

• 批准号: 2733729
• 负责人: PAGE W CAUFIELD
• 金额: $ 35.34万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733729
• 关键词: DNA footprinting; Streptococcus mutans; antibiotics; bacterial genetics; bacterial proteins; gel mobility shift assay; gene expression; genetic manipulation; genetic promoter element; northern blottings; nuclear magnetic resonance spectroscopy; operon; oral bacteria; peptides; protein biosynthesis; protein engineering; protein structure function; reporter genes; site directed mutagenesis; yeast two hybrid system

DESCRIPTION (Adapted from the investigator's Abstract): The proposed research is an extension of previous research pursuing the discovery of a novel antibiotic elaborated by the oral cariogenic bacterium Streptococcus mutans. This potent antibiotic, called mutacin, is a member of the growing class of bacterially synthesized peptide antibiotics called lantibiotics. Lantibiotics are ribosomally synthesized and post-translationally modified peptides containing unusual amino acids called lanthionines, and are produced by, and primarily act on, gram-positive bacteria. Because the mutacin peptide and other lantibiotics are DNA-encoded, changes in their expression and composition can be accomplished by site-directed mutagenesis. For example, genetically-engineered analogues of the nascent mutacin molecule can be modified for an enhanced spectrum of activity against specific pathogens. The aims of the present research are to define and characterize the genetic and biochemical aspects of mutacin biosynthesis, to document its antimicrobial activities, and to study the factors involved with the regulation of its production. Taking advantage of a rapidly growing repertoire of molecular biological techniques including site-directed and cassette mutagenesis, each component of the mutacin molecule can be manipulated and its role determined. From this information, the production of mutacin may be enhanced by genetic and protein engineering. It is anticipated that, at the end of the next five years, the genetic and biochemical determinants for mutacin will be understood and significant progress made towards the large scale production for possible therapeutic application can be explored. Clearly, the race to find not only a targeted, specific antimicrobial against the etiological agents of dental caries, but also against the emerging group of drug resistant pathogens underpins the importance of this area of scientific pursuit.

说明(改编自调查人员摘要)：建议的 这项研究是先前研究的延伸，目的是为了发现 口腔致龋菌链球菌研制的新型抗生素 变种人。这种有效的抗生素，被称为突变素，是不断增长的 一类由细菌合成的多肽抗生素，称为抗生素。 抗生素是通过核糖体合成和翻译后修饰的 含有称为羊硫氨酸的不寻常氨基酸的多肽，以及 由革兰氏阳性细菌产生，主要作用于革兰氏阳性细菌。因为 变构肽和其他抗生素是DNA编码的，它们的变化 表达和合成可以通过定点突变来完成。 例如，新生的突变体的基因工程类似物 可以对分子进行修饰，以增强其抗病毒活性 特定的病原体。本研究的目的是界定和 描述突变蛋白生物合成的遗传和生化方面，以 记录其抗菌活性，并研究涉及的因素 随着对其生产的监管。利用快速增长的 不断增长的分子生物技术剧目，包括 定点突变和盒式突变，突变蛋白的每个组成部分 分子是可以操纵的，其作用也是可以确定的。从这个信息来看， 突变蛋白的产生可能通过遗传和蛋白质来提高。 工程学。预计在未来五年结束时， 我们将了解突变蛋白的遗传和生化决定因素 在实现大规模生产方面取得了重大进展 可以探索治疗应用。显然，这场竞赛不仅是为了找到 一种针对牙科病原体的靶向、特异性抗菌剂 还能对抗新出现的耐药病原菌群体 强调了这一科学追求领域的重要性。