Outer membrane biogenesis in Escherichia coli, Neisseria meningitidis, and Helicobacter pylori: paradigm deviations in H. pylori.

Outer membrane biogenesis in Escherichia coli, Neisseria meningitidis, and Helicobacter pylori: paradigm deviations in H. pylori.
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DOI:
10.3389/fcimb.2012.00029
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发表时间:
2012
影响因子:
5.7
通讯作者:
Goldberg JB
Goldberg JB
中科院分区:
医学2区
文献类型:
--
作者:
Liechti G;Goldberg JB

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幽门螺杆菌(Helicobacter pylori)这种细菌病原体能够利用与其外膜(OM)相关或由其外膜分泌的多种因子在人胃的胃黏膜上定植。脂多糖(LPS)和众多外膜蛋白已被证明与黏附以及免疫刺激/免疫逃避有关。在多种动物模型中,这些因子中的许多对于定植和/或致病过程是必不可少的。尽管细菌表面存在如此众多的潜在靶点,但幽门螺杆菌改变其外膜特征的能力限制了针对这些成分中任何单一成分的疫苗或治疗方法的有效性。然而,很明显的是,将大多数这些分子运输到外膜的复合物所含的蛋白质是高度保守的,并且通常是必不可少的。在过去几年中,膜生物发生领域取得了显著进展,现在有可能针对β - 桶状蛋白、脂蛋白和脂多糖运输到外膜的机制进行研究,从而导致细菌适应性丧失以及膜通透性的显著改变。在这篇综述中,我们讨论了脂多糖、脂蛋白和外膜蛋白(OMPs)的外膜运输机制。虽然对这些运输机制的主要研究是在大肠杆菌(Escherichia coli)和脑膜炎奈瑟菌(Neisseria meningitidis)中进行的,但在这里,我们将在ε - 变形菌的遗传背景下介绍这些系统。生物信息学分析表明,像幽门螺杆菌这样的极简基因组为这些基本途径发挥作用所需的最少成分数量提供了见解。有趣的是,在大多数ε - 变形菌中,虽然与脂多糖、脂蛋白和外膜蛋白运输途径相关的内膜和外膜装置似乎都是完整的,但与大肠杆菌相比,大多数与周质空间相关的成分要么缺失,要么几乎无法识别。最终针对这些途径将产生严重限制成分向外膜的传递/运输并阻止细菌感染人类宿主的能力的最终效果。
The bacterial pathogen Helicobacter pylori is capable of colonizing the gastric mucosa of the human stomach using a variety of factors associated with or secreted from its outer membrane (OM). Lipopolysaccharide (LPS) and numerous OM proteins have been shown to be involved in adhesion and immune stimulation/evasion. Many of these factors are essential for colonization and/or pathogenesis in a variety of animal models. Despite this wide array of potential targets present on the bacterial surface, the ability of H. pylori to vary its OM profile limits the effectiveness of vaccines or therapeutics that target any single one of these components. However, it has become evident that the proteins comprising the complexes that transport the majority of these molecules to the OM are highly conserved and often essential. The field of membrane biogenesis has progressed remarkably in the last few years, and the possibility now exists for targeting the mechanisms by which β-barrel proteins, lipoproteins, and LPS are transported to the OM, resulting in loss of bacterial fitness and significant altering of membrane permeability. In this review, the OM transport machinery for LPS, lipoproteins, and outer membrane proteins (OMPs) are discussed. While the principal investigations of these transport mechanisms have been conducted in Escherichia coli and Neisseria meningitidis, here these systems will be presented in the genetic context of ε proteobacteria. Bioinformatic analysis reveals that minimalist genomes, such as that of Helicobacter pylori, offer insight into the smallest number of components required for these essential pathways to function. Interestingly, in the majority of ε proteobacteria, while the inner and OM associated apparatus of LPS, lipoprotein, and OMP transport pathways appear to all be intact, most of the components associated with the periplasmic compartment are either missing or are almost unrecognizable when compared to their E. coli counterparts. Eventual targeting of these pathways would have the net effect of severely limiting the delivery/transport of components to the OM and preventing the bacterium's ability to infect its human host.
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期刊: VIRULENCE
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