Analyzing the molecular mechanism of lipoprotein localization in Brucella.
Analyzing the molecular mechanism of lipoprotein localization in Brucella.
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DOI：
10.3389/fmicb.2015.01189
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发表时间：
2015
影响因子：
5.2
通讯作者：
Crampton MC
中科院分区：
文献类型：
--
作者：
Goolab S;Roth RL;van Heerden H;Crampton MC
细菌脂蛋白具有多种结构和功能，范围从细菌生理到致病过程。由于源自布鲁氏菌的许多脂蛋白被开发为对抗宿主布鲁氏菌感染的潜在疫苗。这些膜蛋白通过多方面的靶向机制从细胞质转运到细胞膜，并在细胞膜外周锚定。尽管许多研究都集中在布鲁氏菌脂蛋白的鉴定和分类以及它们作为治疗布鲁氏菌病候选疫苗的潜在用途上，但这些脂蛋白转运到布鲁氏菌（和其他病原体）外膜（OM）外表面的潜在途径大部分仍然未知。这部分是由于生物体的复杂性和用于逃避宿主免疫系统的规避策略，脂蛋白的生物结构和活性的变化，以及易位机制的复杂性。布鲁氏菌脂蛋白的生物合成途径涉及一个独特的分泌系统，帮助细胞质转运，在细胞质中通过脂化修饰，通过脂蛋白定位机制途径进行分类，然后准备出口到OM。布鲁氏菌表面定位的脂蛋白可能使用脂蛋白翻转酶或β-桶组装复合体进行易位。本文综述了构成OM的一部分的具有特征的布鲁氏菌OM蛋白，包括少数其他具有特征的细菌脂蛋白及其易位机制。革兰氏阴性菌的脂蛋白定位途径将被用作模型，以确定布鲁氏菌脂蛋白定位的空白并推断潜在的途径。特别感兴趣的是在大肠杆菌和流感嗜血杆菌中发现的双重拓扑脂蛋白。这些来自其他革兰氏阴性菌的脂蛋白的定位和拓扑结构得到了很好的表征，可能有助于推断出更好地理解布鲁氏菌易位过程的解决方案。
Bacterial lipoproteins possess diverse structure and functionality, ranging from bacterial physiology to pathogenic processes. As such many lipoproteins, originating from Brucella are exploited as potential vaccines to countermeasure brucellosis infection in the host. These membrane proteins are translocated from the cytoplasm to the cell membrane where they are anchored peripherally by a multifaceted targeting mechanism. Although much research has focused on the identification and classification of Brucella lipoproteins and their potential use as vaccine candidates for the treatment of Brucellosis, the underlying route for the translocation of these lipoproteins to the outer surface of the Brucella (and other pathogens) outer membrane (OM) remains mostly unknown. This is partly due to the complexity of the organism and evasive tactics used to escape the host immune system, the variation in biological structure and activity of lipoproteins, combined with the complex nature of the translocation machinery. The biosynthetic pathway of Brucella lipoproteins involves a distinct secretion system aiding translocation from the cytoplasm, where they are modified by lipidation, sorted by the lipoprotein localization machinery pathway and thereafter equipped for export to the OM. Surface localized lipoproteins in Brucella may employ a lipoprotein flippase or the β-barrel assembly complex for translocation. This review provides an overview of the characterized Brucella OM proteins that form part of the OM, including a handful of other characterized bacterial lipoproteins and their mechanisms of translocation. Lipoprotein localization pathways in gram negative bacteria will be used as a model to identify gaps in Brucella lipoprotein localization and infer a potential pathway. Of particular interest are the dual topology lipoproteins identified in Escherichia coli and Haemophilus influenza. The localization and topology of these lipoproteins from other gram negative bacteria are well characterized and may be useful to infer a solution to better understand the translocation process in Brucella.