Structure and function of lipopeptide antibiotics and of CAMP factor, a bacterial pore-forming toxin

脂肽抗生素和细菌成孔毒素 CAMP 因子的结构和功能

• 批准号: 250265-2013
• 负责人: Palmer, Michael
• 金额: $ 2.19万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629999
• 关键词: Structure; function; lipopeptide; antibiotics; CAMP

The proposed research concerns the mode of action of a medically important antibiotic, daptomycin, as well as the two related lipopeptide antibiotics A54145D and CDA. These antibiotics kill bacteria by attacking and permeabilizing their cell membranes. We will explore the exact nature of this mode of action with biochemical and biophysical methods and define the correlations between function and molecular structure. This will provide useful information for future efforts to modify and improve antimicrobial activity. A second research area included in this proposal concerns a protein toxin produced by a pathogenic bacterium, Streptococcus agalactiae. This toxin, CAMP factor, also damages cell membranes, but in this case the target cell membranes of those of human cells. We will investigate the structure of the toxin-mediated membrane lesion with biochemical and fluorescence methods.

拟议的研究涉及一种医学上重要的抗生素达托霉素以及两种相关的脂肽抗生素A54145D和CDA的作用方式。这些抗生素通过攻击和渗透细菌的细胞膜来杀死细菌。我们将用生物化学和生物物理学方法探索这种作用模式的确切性质，并定义功能和分子结构之间的相关性。这将为今后改进和提高抗微生物活性提供有用的信息。该提案中包括的第二个研究领域涉及由致病细菌无乳链球菌产生的蛋白质毒素。这种毒素，CAMP因子，也破坏细胞膜，但在这种情况下，人类细胞的靶细胞膜。我们将用生化和荧光方法研究毒素介导的膜损伤的结构。