Postsynthetic Modifications of Bacterial Membrane Lipids

细菌膜脂质的合成后修饰

• 批准号: 6838207
• 负责人: John E. Cronan
• 金额: $ 22.19万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6838207
• 关键词: Salmonella typhimurium; cis trans isomerization; cyclization; cyclopropanes; isomer; isomerase; laboratory mouse; lipid bilayer membrane; lipid biosynthesis; membrane biogenesis; membrane lipids; membrane permeability

DESCRIPTION (provided by applicant): This proposal is to study the biosynthesis, function, regulation, and possible role in bacterial pathogenesis of two modifications that alter the membrane phospholipid bilayers of bacteria. Both modifications alter the cis double bonds of the unsaturated acyl chains of the lipids after the lipids have been synthesized, deposited, and are functioning in the cell membranes. One of these modifications, cis-trans isomerization, is limited to a few families of bacteria whereas the other, cyclopropane ring formation is found in a very wide range of diverse bacteria. Both lipid modifications increase the resistance of the bacterium to environmental stresses. For example, cyclopropane ring formation increases resistance to acid conditions and may be of importance in survival of a water-borne pathogen as it passes through the stomach. Cis-trans isomerization results in improved fitness for growth at high temperature and resistance to certain toxic compounds. Both modifications are conserved in numerous pathogens and cyclopropane ring formation has been ascribed a role in Mycobacterium tuberculosis pathogenesis. These processes will be studied by a combination of biochemical, genetic, and molecular biological approaches including tests of pathogenesis in a mouse model system

描述（由申请人提供）：该建议是研究两种修饰的细菌发病机理中的生物合成，功能，调节和可能的作用，这些修饰改变了细菌的膜磷脂双层。两种修饰都会改变脂质的不饱和酰基链的顺式双键在脂质被合成，沉积并在细胞膜中起作用。这些修饰之一，即顺式跨性异构化，仅限于细菌的几个家族，而另一个环丙烷环形成在非常广泛的多种细菌中。两种脂质修饰都会增加细菌对环境应力的抗性。例如，环丙烷环的形成增加了对酸性条件的抵抗力，并且在水通过胃的生存中可能很重要。顺式传播异构化可提高高温下生长的适应性和对某些有毒化合物的耐药性。这两种修饰都是在许多病原体中保守的，环丙烷环的形成已在结核分枝杆菌发病机理中起作用。这些过程将通过生化，遗传和分子生​​物学方法的组合进行研究，包括小鼠模型系统中的发病机理测试