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

这项拟议的研究涉及一种重要的医学抗生素达托霉素的作用模式，以及两种相关的脂肽抗生素A54145D和CDA。这些抗生素通过攻击和渗透细菌的细胞膜来杀死细菌。我们将用生化和生物物理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关系。这将为今后修改和改进抗菌剂活性的努力提供有用的信息。 这项建议中包括的第二个研究领域涉及一种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，也会破坏细胞膜，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。

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.