Outer membrane biogenesis in E. coli, Neisseria meningitidis, and Helicobacter pylori; paradigm deviations in H. pylori

Department of Microbiology, Immunology, and Cancer Biology, University of Virginia Health System, Charlottesville VA, USA.
Frontiers in Cellular and Infection Microbiology (Impact Factor: 3.72). 04/2012; 2:29. DOI: 10.3389/fcimb.2012.00029
Source: PubMed


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 outer membrane 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 outer membrane profile limits the effectiveness of vaccines that use 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 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 outer membrane associated apparatus of LPS, lipoprotein, and OM protein 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

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Available from: George Liechti, Apr 29, 2014
    • "similar structure as LptC consisting of an N-terminal α-helix with the rest of the protein consisting of β-sheet; only, a small α-helix was additionally predicted with low confidence level at the C-terminus of HP1569 (see Fig. S1, Supporting Information). Indeed, the structure of an N-terminal portion of HP1569 could be modeled using E. coli LptC as a template (Liechti and Goldberg 2012). Thus, HP1569 could be the functional homolog of LptC in H. pylori. "
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    ABSTRACT: Lipopolysaccharides (LPS) are major lipidic components of the outer membrane of most Gram-negative bacteria. They form a permeability barrier that protects these bacteria from harmful compounds in the environment. In addition, they are important signaling molecules for the innate immune system. The mechanism of transport of these molecules to the bacterial cell surface has remained enigmatic for a long time. However, intense research during the last decade, particularly in Escherichia coli and Neisseria meningitidis, has led to the identification of the machinery that mediates LPS transport. In this review, we summarize the current knowledge of the LPS transport machinery and provide an overview of the distribution of the components of this machinery among diverse bacteria, even organisms that don't produce LPS. We also discuss the current insights in the regulation of LPS biosynthesis. © FEMS 2015. All rights reserved. For permissions, please e-mail:
    No preview · Article · Jun 2015 · FEMS microbiology reviews
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    • "Pathogenic bacteria also acquire many virulence determinants which enable specialized niche adaptation. A recent study by Liechti and Goldberg (2012) has shown that genome reduction and niche specialization in H. pylori has resulted in a smaller number of components required for OMP, LPS, and lipoprotein transport pathways. In this review, the periplasmic protein folding and LPS biogenesis pathways of the extensively studied commensal E. coli, and epidemic pathogen, Neisseria meningitidis , are compared. "
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    ABSTRACT: The Gram-negative bacterial cell envelope consists of an inner membrane (IM) that surrounds the cytoplasm and an asymmetrical outer-membrane (OM) that forms a protective barrier to the external environment. The OM consists of lipopolysaccahride (LPS), phospholipids, outer membrane proteins (OMPs), and lipoproteins. Oxidative protein folding mediated by periplasmic oxidoreductases is required for the biogenesis of the protein components, mainly constituents of virulence determinants such as pili, flagella, and toxins, of the Gram-negative OM. Recently, periplasmic oxidoreductases have been implicated in LPS biogenesis of Escherichia coli and Neisseria meningitidis. Differences in OM biogenesis, in particular the transport pathways for endotoxin to the OM, the composition and role of the protein oxidation, and isomerization pathways and the regulatory networks that control them have been found in these two Gram-negative species suggesting that although form and function of the OM is conserved, the pathways required for the biosynthesis of the OM and the regulatory circuits that control them have evolved to suit the lifestyle of each organism.
    Full-text · Article · Dec 2012 · Frontiers in Cellular and Infection Microbiology
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    Full-text · Article · Dec 2012 · Frontiers in Cellular and Infection Microbiology
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