Postsynthetic Modifications of Bacterial Membrane Lipids

描述(申请人提供)：本提案旨在研究改变细菌膜磷脂双层的两种修饰的生物合成、功能、调节以及在细菌发病机制中的可能作用。在脂类合成、沉积并在细胞膜中发挥作用后，这两种修饰都会改变脂类的不饱和酰链的顺式双键。其中一种修饰是顺反异构化，仅限于几个细菌家族，而另一种修饰是环丙烷环的形成，在非常广泛的不同细菌中发现。这两种脂类修饰都提高了细菌对环境压力的抵抗力。例如，环丙烷环的形成增强了对酸性条件的抵抗力，在水传播的病原体通过胃时可能对其生存至关重要。顺反异构化提高了植物在高温下生长的适宜性和对某些有毒化合物的抵抗力。这两种修饰在许多病原体中都是保守的，环丙烷环的形成被认为在结核分枝杆菌的发病机制中起到了作用。这些过程将通过生物化学、遗传学和分子生物学相结合的方法进行研究，包括在小鼠模型系统中进行发病机制测试。

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