Postsynthetic Modifications of Bacterial Membrane Lipids

描述（由申请人提供）：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、调节和在细菌发病机制中的可能作用。这两种修饰都改变了脂质合成、沉积并在细胞膜中发挥作用后脂质不饱和酰基链的顺式双键。这些修改之一，顺-反异构化，是有限的几个家庭的细菌，而另一个，环丙烷环的形成被发现在一个非常广泛的不同的细菌。这两种脂质修饰都增加了细菌对环境胁迫的抵抗力。例如，环丙烷环的形成增加了对酸性条件的抵抗力，并且可能对水传播病原体通过胃时的生存至关重要。顺-反异构化导致在高温下生长的适应性提高和对某些有毒化合物的抗性。这两种修饰在许多病原体中是保守的，并且环丙烷环的形成被认为在结核分枝杆菌的发病机制中起作用。这些过程将通过生物化学，遗传学和分子生物学方法的组合进行研究，包括在小鼠模型系统中进行发病机制的测试

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