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Lipopolysaccharides (LPSs) 2018

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (29 October 2018) | Viewed by 53127

Special Issue Editor

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our 2017 Special Issue, "Lipopolysaccharides (LPSs)" (https://www.mdpi.com/journal/ijms/special_issues/LPSs).

In Gram-negative bacteria, three layers surround the cytoplasm: An inner membrane, a layer of peptidoglycan, and an outer membrane. The outer membrane is an asymmetric lipidic bilayer, with phospholipids on its inner surface, and lipopolysaccharides (LPSs) on the outside, this being the major component of the outer leaflet, covering approximately nearly three quarters of the total outer cell surface.
All LPSs possess the same general chemical architecture, independently of the bacterial activity (pathogenic, symbiotic, commensal), ecological niches (human, animal, soil, plant, water), or growth conditions. Endotoxins are large amphiphilic molecules consisting of a hydrophilic polysaccharide part, and a covalently bound hydrophobic and highly conserved lipid component, termed lipid A (the endotoxin subunit). The polysaccharide part can be divided into two sub-domains: The internal and conserved, the core region, and one more external and highly variable, the O-specific chain, also named O-antigen for its immunogenic properties. LPSs are endotoxins, one of the most potent classes of activators of the mammalian immune system; they can be released from cell surfaces of bacteria during their multiplication, lysis, and death. LPS can acts through its biological center (lipid A component) on various cell types, of which macrophages and monocytes are the most important.

Prof. Dr. Juan M. Tomás
Guest Editor

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Keywords

  • biosynthesis 
  • assembly 
  • chemical structure
  • biological significance 
  • genetics 
  • modifications 
  • immunity 
  • vaccines

Published Papers (8 papers)

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Research

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20 pages, 5264 KiB  
Article
Neuroimmunological Implications of Subclinical Lipopolysaccharide from Salmonella Enteritidis
by Anita Mikołajczyk and Dagmara Złotkowska
Int. J. Mol. Sci. 2018, 19(10), 3274; https://doi.org/10.3390/ijms19103274 - 22 Oct 2018
Cited by 11 | Viewed by 3622
Abstract
Mounting evidence has indicated that lipopolysaccharide (LPS) is implicated in neuroimmunological responses, but the body’s response to subclinical doses of bacterial endotoxin remains poorly understood. The influence of a low single dose of LPS from Salmonella Enteritidis, which does not result in any [...] Read more.
Mounting evidence has indicated that lipopolysaccharide (LPS) is implicated in neuroimmunological responses, but the body’s response to subclinical doses of bacterial endotoxin remains poorly understood. The influence of a low single dose of LPS from Salmonella Enteritidis, which does not result in any clinical symptoms of intoxication (subclinical lipopolysaccharide), on selected cells and signal molecules of the neuroimmune system was tested. Five juvenile crossbred female pigs were intravenously injected with LPS from S. Enteritidis (5 μg/kg body weight (b.w.)), while five pigs from the control group received sodium chloride in the same way. Our data demonstrated that subclinical LPS from S. Enteritidis increased levels of dopamine in the brain and neuropeptides such as substance P (SP), galanin (GAL), neuropeptide Y (NPY), and active intestinal peptide (VIP) in the cervical lymph nodes with serum hyperhaptoglobinaemia and reduction of plasma CD4 and CD8 T-lymphocytes seven days after lipopolysaccharide administration. CD4 and CD8 T-lymphocytes from the cervical lymph node and serum interleukin-6 and tumour necrosis factor α showed no significant differences between the control and lipopolysaccharide groups. Subclinical lipopolysaccharide from S. Enteritidis can affect cells and signal molecules of the neuroimmune system. The presence of subclinical lipopolysaccharide from S. Enteritidis is associated with unknown prolonged consequences and may require eradication and a deeper search into the asymptomatic carrier state of Salmonella spp. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs) 2018)
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23 pages, 6249 KiB  
Article
Effects of 1-Methyltryptophan on Immune Responses and the Kynurenine Pathway after Lipopolysaccharide Challenge in Pigs
by Elisa Wirthgen, Winfried Otten, Margret Tuchscherer, Armin Tuchscherer, Grazyna Domanska, Julia Brenmoehl, Juliane Günther, Daniela Ohde, Werner Weitschies, Anne Seidlitz, Eberhard Scheuch and Ellen Kanitz
Int. J. Mol. Sci. 2018, 19(10), 3009; https://doi.org/10.3390/ijms19103009 - 02 Oct 2018
Cited by 11 | Viewed by 4554
Abstract
An enhanced indoleamine 2,3-dioxygenase 1 (IDO1) activity is associated with an increased mortality risk in sepsis patients. Thus, the preventive inhibition of IDO1 activity may be a promising strategy to attenuate the severity of septic shock. 1-methyltryptophan (1-MT) is currently in the interest [...] Read more.
An enhanced indoleamine 2,3-dioxygenase 1 (IDO1) activity is associated with an increased mortality risk in sepsis patients. Thus, the preventive inhibition of IDO1 activity may be a promising strategy to attenuate the severity of septic shock. 1-methyltryptophan (1-MT) is currently in the interest of research due to its potential inhibitory effects on IDO1 and immunomodulatory properties. The present study aims to investigate the protective and immunomodulatory effects of 1-methyltryptophan against endotoxin-induced shock in a porcine in vivo model. Effects of 1-MT were determined on lipopolysaccharide (LPS)-induced tryptophan (TRP) degradation, immune response and sickness behaviour. 1-MT increased TRP and its metabolite kynurenic acid (KYNA) in plasma and tissues, suppressed the LPS-induced maturation of neutrophils and increased inactivity of the animals. 1-MT did not inhibit the LPS-induced degradation of TRP to kynurenine (KYN)—a marker for IDO1 activity—although the increase in KYNA indicates that degradation to one branch of the KYN pathway is facilitated. In conclusion, our findings provide no evidence for IDO1 inhibition but reveal the side effects of 1-MT that may result from the proven interference of KYNA and 1-MT with aryl hydrocarbon receptor signalling. These effects should be considered for therapeutic applications of 1-MT. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs) 2018)
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17 pages, 1816 KiB  
Article
Distribution and Neurochemistry of the Porcine Ileocaecal Valve Projecting Sensory Neurons in the Dorsal Root Ganglia and the Influence of Lipopolysaccharide from Different Serotypes of Salmonella spp. on the Chemical Coding of DRG Neurons in the Cell Cultures
by Anita Mikołajczyk, Anna Kozłowska and Sławomir Gonkowski
Int. J. Mol. Sci. 2018, 19(9), 2551; https://doi.org/10.3390/ijms19092551 - 28 Aug 2018
Cited by 8 | Viewed by 3973
Abstract
The ileocecal valve (ICV)—a sphincter muscle between small and large intestine—plays important roles in the physiology of the gastrointestinal (GI) tract, but many aspects connected with the innervation of the ICV remain unknown. Thus, the aim of this study was to investigate the [...] Read more.
The ileocecal valve (ICV)—a sphincter muscle between small and large intestine—plays important roles in the physiology of the gastrointestinal (GI) tract, but many aspects connected with the innervation of the ICV remain unknown. Thus, the aim of this study was to investigate the localization and neurochemical characterization of neurons located in the dorsal root ganglia and supplying the ICV of the domestic pig. The results have shown that such neurons mainly located in the dorsal root ganglia (DRG) of thoracic and lumbar neuromers show the presence of substance P (SP), calcitonin gene-related peptide (CGRP), and galanin (GAL). The second part of the experiment consisted of a study on the influence of a low dose of lipopolysaccharide (LPS) from Salmonella serotypes Enteritidis Minnesota and Typhimurium on DRG neurons. It has been shown that the LPS of these serotypes in studied doses does not change the number of DRG neurons in the cell cultures, but influences the immunoreactivity to SP and GAL. The observed changes in neurochemical characterization depend on the bacterial serotype. The results show that DRG neurons take part in the innervation of the ICV and may change their neurochemical characterization under the impact of LPS, which is probably connected with direct actions of this substance on the nervous tissue and/or its pro-inflammatory activity. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs) 2018)
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19 pages, 4694 KiB  
Article
Glycine Relieves Intestinal Injury by Maintaining mTOR Signaling and Suppressing AMPK, TLR4, and NOD Signaling in Weaned Piglets after Lipopolysaccharide Challenge
by Xiao Xu, Xiuying Wang, Huanting Wu, Huiling Zhu, Congcong Liu, Yongqing Hou, Bing Dai, Xiuting Liu and Yulan Liu
Int. J. Mol. Sci. 2018, 19(7), 1980; https://doi.org/10.3390/ijms19071980 - 06 Jul 2018
Cited by 30 | Viewed by 6762
Abstract
This study was conducted to envaluate whether glycine could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury by regulating intestinal epithelial energy status, protein synthesis, and inflammatory response via AMPK, mTOR, TLR4, and NOD signaling pathways. A total of 24 weanling piglets were randomly [...] Read more.
This study was conducted to envaluate whether glycine could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury by regulating intestinal epithelial energy status, protein synthesis, and inflammatory response via AMPK, mTOR, TLR4, and NOD signaling pathways. A total of 24 weanling piglets were randomly allotted to 1 of 4 treatments: (1) non-challenged control; (2) LPS-challenged control; (3) LPS + 1% glycine; (4) LPS + 2% glycine. After 28 days feeding, piglets were injected intraperitoneally with saline or LPS. The pigs were slaughtered and intestinal samples were collected at 4 h postinjection. The mRNA expression of key genes in these signaling pathways was measured by real-time PCR. The protein abundance was measured by Western blot analysis. Supplementation with glycine increased jejunal villus height/crypt depth ratio. Glycine also increased the jejunal and ileal protein content, RNA/DNA ratio, and jejunal protein/DNA ratio. The activities of citroyl synthetase in ileum, and α-ketoglutarate dehydrogenase complex in jejunum, were increased in the piglets fed diets supplemented with glycine. In addition, glycine decreased the jejunal and ileal phosphorylation of AMPKα, and increased ileal phosphorylation of mTOR. Furthermore, glycine downregulated the mRNA expression of key genes in inflammatory signaling. Meanwhile, glycine increased the mRNA expression of negative regulators of inflammatory signaling. These results indicate that glycine supplementation could improve energy status and protein synthesis by regulating AMPK and mTOR signaling pathways, and relieve inflammation by inhibiting of TLR4 and NOD signaling pathways to alleviate intestinal injury in LPS-challenged piglets. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs) 2018)
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Review

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17 pages, 1853 KiB  
Review
Immune Mechanisms Underlying Susceptibility to Endotoxin Shock in Aged Hosts: Implication in Age-Augmented Generalized Shwartzman Reaction
by Manabu Kinoshita, Masahiro Nakashima, Hiroyuki Nakashima and Shuhji Seki
Int. J. Mol. Sci. 2019, 20(13), 3260; https://doi.org/10.3390/ijms20133260 - 02 Jul 2019
Cited by 7 | Viewed by 6259
Abstract
In recent decades, the elderly population has been rapidly increasing in many countries. Such patients are susceptible to Gram-negative septic shock, namely endotoxin shock. Mortality due to endotoxin shock remains high despite recent advances in medical care. The generalized Shwartzman reaction is well [...] Read more.
In recent decades, the elderly population has been rapidly increasing in many countries. Such patients are susceptible to Gram-negative septic shock, namely endotoxin shock. Mortality due to endotoxin shock remains high despite recent advances in medical care. The generalized Shwartzman reaction is well recognized as an experimental endotoxin shock. Aged mice are similarly susceptible to the generalized Shwartzman reaction and show an increased mortality accompanied by the enhanced production of tumor necrosis factor (TNF). Consistent with the findings in the murine model, the in vitro Shwartzman reaction-like response is also age-dependently augmented in human peripheral blood mononuclear cells, as assessed by enhanced TNF production. Interestingly, age-dependently increased innate lymphocytes with T cell receptor-that intermediate expression, such as that of CD8+CD122+T cells in mice and CD57+T cells in humans, may collaborate with macrophages and induce the exacerbation of the Shwartzman reaction in elderly individuals. However, endotoxin tolerance in mice, which resembles a mirror phenomenon of the generalized Shwartzman reaction, drastically reduces the TNF production of macrophages while strongly activating their bactericidal activity in infection. Importantly, this effect can be induced in aged mice. The safe induction of endotoxin tolerance may be a potential therapeutic strategy for refractory septic shock in elderly patients. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs) 2018)
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31 pages, 436 KiB  
Review
Lipopolysaccharide-Induced Neuroinflammation as a Bridge to Understand Neurodegeneration
by Carla Ribeiro Alvares Batista, Giovanni Freitas Gomes, Eduardo Candelario-Jalil, Bernd L. Fiebich and Antonio Carlos Pinheiro de Oliveira
Int. J. Mol. Sci. 2019, 20(9), 2293; https://doi.org/10.3390/ijms20092293 - 09 May 2019
Cited by 263 | Viewed by 11895
Abstract
A large body of experimental evidence suggests that neuroinflammation is a key pathological event triggering and perpetuating the neurodegenerative process associated with many neurological diseases. Therefore, different stimuli, such as lipopolysaccharide (LPS), are used to model neuroinflammation associated with neurodegeneration. By acting at [...] Read more.
A large body of experimental evidence suggests that neuroinflammation is a key pathological event triggering and perpetuating the neurodegenerative process associated with many neurological diseases. Therefore, different stimuli, such as lipopolysaccharide (LPS), are used to model neuroinflammation associated with neurodegeneration. By acting at its receptors, LPS activates various intracellular molecules, which alter the expression of a plethora of inflammatory mediators. These factors, in turn, initiate or contribute to the development of neurodegenerative processes. Therefore, LPS is an important tool for the study of neuroinflammation associated with neurodegenerative diseases. However, the serotype, route of administration, and number of injections of this toxin induce varied pathological responses. Thus, here, we review the use of LPS in various models of neurodegeneration as well as discuss the neuroinflammatory mechanisms induced by this toxin that could underpin the pathological events linked to the neurodegenerative process. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs) 2018)
22 pages, 1773 KiB  
Review
Regulated Assembly of LPS, Its Structural Alterations and Cellular Response to LPS Defects
by Gracjana Klein and Satish Raina
Int. J. Mol. Sci. 2019, 20(2), 356; https://doi.org/10.3390/ijms20020356 - 16 Jan 2019
Cited by 71 | Viewed by 9705
Abstract
Distinguishing feature of the outer membrane (OM) of Gram-negative bacteria is its asymmetry due to the presence of lipopolysaccharide (LPS) in the outer leaflet of the OM and phospholipids in the inner leaflet. Recent studies have revealed the existence of regulatory controls that [...] Read more.
Distinguishing feature of the outer membrane (OM) of Gram-negative bacteria is its asymmetry due to the presence of lipopolysaccharide (LPS) in the outer leaflet of the OM and phospholipids in the inner leaflet. Recent studies have revealed the existence of regulatory controls that ensure a balanced biosynthesis of LPS and phospholipids, both of which are essential for bacterial viability. LPS provides the essential permeability barrier function and act as a major virulence determinant. In Escherichia coli, more than 100 genes are required for LPS synthesis, its assembly at inner leaflet of the inner membrane (IM), extraction from the IM, translocation to the OM, and in its structural alterations in response to various environmental and stress signals. Although LPS are highly heterogeneous, they share common structural elements defining their most conserved hydrophobic lipid A part to which a core polysaccharide is attached, which is further extended in smooth bacteria by O-antigen. Defects or any imbalance in LPS biosynthesis cause major cellular defects, which elicit envelope responsive signal transduction controlled by RpoE sigma factor and two-component systems (TCS). RpoE regulon members and specific TCSs, including their non-coding arm, regulate incorporation of non-stoichiometric modifications of LPS, contributing to LPS heterogeneity and impacting antibiotic resistance. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs) 2018)
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12 pages, 1120 KiB  
Review
Structural Basis for the Lipopolysaccharide Export Activity of the Bacterial Lipopolysaccharide Transport System
by Greg Hicks and Zongchao Jia
Int. J. Mol. Sci. 2018, 19(9), 2680; https://doi.org/10.3390/ijms19092680 - 10 Sep 2018
Cited by 29 | Viewed by 5803
Abstract
Gram-negative bacteria have a dense outer membrane (OM) coating of lipopolysaccharides, which is essential to their survival. This coating is assembled by the LPS (lipopolysaccharide) transport (Lpt) system, a coordinated seven-subunit protein complex that spans the cellular envelope. LPS transport is driven by [...] Read more.
Gram-negative bacteria have a dense outer membrane (OM) coating of lipopolysaccharides, which is essential to their survival. This coating is assembled by the LPS (lipopolysaccharide) transport (Lpt) system, a coordinated seven-subunit protein complex that spans the cellular envelope. LPS transport is driven by an ATPase-dependent mechanism dubbed the “PEZ” model, whereby a continuous stream of LPS molecules is pushed from subunit to subunit. This review explores recent structural and functional findings that have elucidated the subunit-scale mechanisms of LPS transport, including the novel ABC-like mechanism of the LptB2FG subcomplex and the lateral insertion of LPS into the OM by LptD/E. New questions are also raised about the functional significance of LptA oligomerization and LptC. The tightly regulated interactions between these connected subcomplexes suggest a pathway that can react dynamically to membrane stress and may prove to be a valuable target for new antibiotic therapies for Gram-negative pathogens. Full article
(This article belongs to the Special Issue Lipopolysaccharides (LPSs) 2018)
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