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螺旋体脂蛋白在发病机制和免疫中的作用。

Spirochetal Lipoproteins in Pathogenesis and Immunity.

机构信息

Division of Infectious Diseases, VA Greater Los Angeles Healthcare System, Los Angeles, CA, 90073, USA.

Departments of Medicine, Urology, and Microbiology, Immunology, and Molecular Genetics, The David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.

出版信息

Curr Top Microbiol Immunol. 2018;415:239-271. doi: 10.1007/82_2017_78.

DOI:10.1007/82_2017_78
PMID:29196824
Abstract

Lipoproteins are lipid-modified proteins that dominate the spirochetal proteome. While found in all bacteria, spirochetal lipoproteins have unique features and play critical roles in spirochete biology. For this reason, considerable effort has been devoted to determining how the lipoproteome is generated. Essential features of the structural elements of lipoproteins are now understood with greater clarity, enabling greater confidence in identification of lipoproteins from genomic sequences. The journey from the ribosome to the outer membrane, and in some cases, to the cellular surface has been defined, including secretion, lipidation, sorting, and export across the outer membrane. Given their abundance and importance, it is not surprising that spirochetes have developed a number of strategies for regulating the spatiotemporal expression of lipoproteins. In some cases, lipoprotein expression is tied to various environmental cues, while in other cases, it is linked to growth rate. This regulation enables spirochetes to express certain lipoproteins at high levels in one phase of the spirochete lifecycle, while dramatically downregulating the same lipoproteins in other phases. The mammalian host has developed specialized mechanisms for recognizing lipoproteins and triggering an immune response. Evasion of that immune response is essential for spirochete persistence. For this reason, spirochetes have developed mechanisms for altering lipoproteins. Lipoproteins recognized by antibodies formed during infection are key serodiagnostic antigens. In addition, lipoprotein vaccines have been developed for generating an immune response to control or prevent a spirochete infection. This chapter summarizes our current understanding of lipoproteins in interactions of spirochetes with their hosts.

摘要

脂蛋白是经过脂质修饰的蛋白质,它们在螺旋体的蛋白质组中占主导地位。虽然在所有细菌中都发现了螺旋体脂蛋白,但它们具有独特的特征,在螺旋体生物学中发挥着关键作用。因此,人们投入了相当大的精力来确定脂蛋白组是如何产生的。现在,人们对脂蛋白结构元素的基本特征有了更清晰的认识,从而在从基因组序列中识别脂蛋白时更有信心。从核糖体到外膜,在某些情况下,到细胞表面的旅程已经被定义,包括分泌、脂质化、分拣和穿过外膜的输出。由于它们的丰富度和重要性,螺旋体已经开发出了许多调节脂蛋白时空表达的策略也就不足为奇了。在某些情况下,脂蛋白的表达与各种环境线索有关,而在其他情况下,它与生长速度有关。这种调节使螺旋体能够在螺旋体生命周期的一个阶段高水平表达某些脂蛋白,而在其他阶段则显著下调相同的脂蛋白。哺乳动物宿主已经开发出专门的机制来识别脂蛋白并触发免疫反应。逃避这种免疫反应对螺旋体的持续存在至关重要。出于这个原因,螺旋体已经开发出了改变脂蛋白的机制。在感染过程中形成的抗体识别的脂蛋白是关键的血清诊断抗原。此外,已经开发出脂蛋白疫苗来产生免疫反应以控制或预防螺旋体感染。本章总结了我们目前对螺旋体与宿主相互作用中脂蛋白的理解。

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