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Toxins
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Lipopolysaccharide: Bacterial Endotoxin
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Lipopolysaccharide: Bacterial Endotoxin

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (30 November 2018) | Viewed by 40712

Special Issue Editor

Prof. Dr. Susana Merino Montero

E-Mail Website
Guest Editor
Department of Genetic, Microbiology and Statistic, University of Barcelona, 08028 Barcelona, Spain
Interests: lipopolysaccharide; genomics; proteomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is my pleasure to invite you to submit an original or review article for publication in a Special Issue on “Lipopolysaccharide: Bacterial Endotoxin”.

Lipopolysaccharide (LPS) is the major molecular surface component of the outer membrane of Gram-negative bacteria. LPSs are negatively-charged molecules exposed to the external environment and that provide a physical barrier that protects bacteria from antibacterial agents. They are amphiphilic molecules, consisting of a hydrophilic polysaccharide or oligosaccharide portion, covalently linked to a hydrophobic and high conserved lipid portion, termed lipid A, which is embedded in the external face of the outer membrane. The saccharide portion is diverse in terms of length and composition among different Gram-negative bacterial species, and can be divided in two domains: The core, which can be subdivided into inner and outer cores, and the O-antigen chain. The inner core is proximal to lipid A, which is required for bacterial viability, and contains unusual sugars, such as 3-deoxy-D-manno-octulosonic acid (Kdo) and heptoses. However, the outer core typically contains hexose sugars. The O-antigen chain is the most external domain, is highly variable, and is composed of repeating oligosaccharide units.

The LPS lipid A released from cell surfaces of bacteria during multiplication, lysis or death can be recognized by specific host cell receptors and is responsible for the activation of the innate immune system via the induction of inflammatory cytokines release. The uncontrolled activation of innate immune response triggers the development of septic shock and multiple-organ failure. Thus, lipid A is one of the most potent immune-stimulators, of which the toxicity depends on its primary structure and the severity of infection. Although lipid A is highly conserved biochemically, some bacteria show an impressive amount of diversity. Variations of the lipid A serve to promote survival by providing resistance to components of the innate immune system and help to evade recognition by Toll-like receptors.

The set of articles proposed for this Special Issue will examine the structure and composition, biological activity, host interaction, and induction of innate immunity of the Gram-negative bacterial endotoxin.

Prof. Susana Merino Montero
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Lipid A
  • Core LPS
  • O-antigen LPS
  • Glycoconjugates
  • Chemical structure
  • Biological significance
  • Host interaction
  • Immune evasion
  • vaccines

Published Papers (7 papers)

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Research

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15 pages, 2323 KiB  
Article
Bacterial Lipopolysaccharide Induced Alterations of Genome-Wide DNA Methylation and Promoter Methylation of Lactation-Related Genes in Bovine Mammary Epithelial Cells
by Jingbo Chen, Yongjiang Wu, Yawang Sun, Xianwen Dong, Zili Wang, Zhu Zhang, Yanli Xiao and Guozhong Dong
Toxins 2019, 11(5), 298; https://doi.org/10.3390/toxins11050298 - 24 May 2019
Cited by 30 | Viewed by 3179
Abstract
Bacterial lipopolysaccharide (LPS) could result in poor lactation performance in dairy cows. High methylation of DNA is associated with gene repression. However, it is unclear whether LPS could suppress the expression of lactation-related genes by inducing DNA methylation. Therefore, the objective of this [...] Read more.
Bacterial lipopolysaccharide (LPS) could result in poor lactation performance in dairy cows. High methylation of DNA is associated with gene repression. However, it is unclear whether LPS could suppress the expression of lactation-related genes by inducing DNA methylation. Therefore, the objective of this study was to investigate the impact of LPS on genome-wide DNA methylation, using methylated DNA immunoprecipitation with high-throughput sequencing (MeDIP-seq) and on the promoter methylation of lactation-related genes using MassArray analysis in bovine mammary epithelial cells. The bovine mammary epithelial cell line MAC-T cells were treated for 48 h with LPS at different doses of 0, 1, 10, 100, and 1000 endotoxin units (EU)/mL (1 EU = 0.1 ng). The results showed that the genomic methylation levels and the number of methylated genes in the genome as well as the promoter methylation levels of milk genes increased when the LPS dose was raised from 0 to 10 EU/mL, but decreased after further increasing the LPS dose. The milk gene mRNA expression levels of the 10 EU/mL LPS treatment were significantly lower than these of untreated cells. The results also showed that the number of hypermethylated genes was greater than that of hypomethylated genes in lipid and amino acid metabolic pathways following 1 and 10 EU/mL LPS treatments as compared with control. By contrast, in the immune response pathway the number of hypomethylated genes increased with increasing LPS doses. The results indicate LPS at lower doses induced hypermethylation of the genome and promoters of lactation-related genes, affecting milk gene mRNA expression. However, LPS at higher doses induced hypomethylation of genes involved in the immune response pathway probably in favor of immune responses. Full article
(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin)
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13 pages, 3448 KiB  
Article
Investigation into Cellular Glycolysis for the Mechanism Study of Energy Metabolism Disorder Triggered by Lipopolysaccharide
by Ruyuan Zhang, Jian Ji, Ivana Blaženović, Fuwei Pi, Tingwei Wang, Yinzhi Zhang and Xiulan Sun
Toxins 2018, 10(11), 441; https://doi.org/10.3390/toxins10110441 - 29 Oct 2018
Cited by 5 | Viewed by 3617
Abstract
Lipopolysaccharide (LPS) is the main virulence factor of Gram-negative bacteria, which can incite inflammation in tissues by inducing cells to secrete a variety of proinflammatory mediators, including cytokines, chemokines, interleukins, and prostaglandins. Herein, we chose LPS as an inducer to establish an inflammatory [...] Read more.
Lipopolysaccharide (LPS) is the main virulence factor of Gram-negative bacteria, which can incite inflammation in tissues by inducing cells to secrete a variety of proinflammatory mediators, including cytokines, chemokines, interleukins, and prostaglandins. Herein, we chose LPS as an inducer to establish an inflammatory model of HeLa cells, and explored the effects of LPS on energy metabolism. We treated HeLa cells with different concentrations (0, 0.4, 1.0, 2.0, 4.0, and 6.0 μg/mL) of LPS for 24 h, and explored its effects on intercellular adenosine triphosphate (ATP) levels, intercellular nitrous oxide (NO) content, mitochondrial functions, and enzyme activities related to energy metabolism. Furthermore, we used metabonomics to study the metabolites that participated in energy metabolism. We found a positive correlation between LPS concentrations and intracellular ATP levels. In addition, LPS increased intracellular NO production, altered mitochondrial functions, strengthened glycolytic enzyme activities, and changed metabolites related to energy metabolism. Hence, in this study, we showed that LPS can strengthen energy metabolism by enhancing glycolysis, which could be used as an early diagnostic biomarker or a novel therapeutic target for inflammation-associated cancers. Full article
(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin)
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12 pages, 1340 KiB  
Article
The Effect of Cyanobacterial LPS Antagonist (CyP) on Cytokines and Micro-RNA Expression Induced by Porphyromonas gingivalis LPS
by Monica Molteni, Annalisa Bosi and Carlo Rossetti
Toxins 2018, 10(7), 290; https://doi.org/10.3390/toxins10070290 - 16 Jul 2018
Cited by 12 | Viewed by 3987
Abstract
Lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg-LPS) is a key bacterial structure involved in the maintenance of a chronic pro-inflammatory environment during periodontitis. Similar to other gram-negative LPS, Pg-LPS induces the release of pro-inflammatory cytokines through interaction with Toll-Like Receptor 4 (TLR4) and is [...] Read more.
Lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg-LPS) is a key bacterial structure involved in the maintenance of a chronic pro-inflammatory environment during periodontitis. Similar to other gram-negative LPS, Pg-LPS induces the release of pro-inflammatory cytokines through interaction with Toll-Like Receptor 4 (TLR4) and is able to stimulate negative TLR4 regulatory pathways, such as those involving microRNA (miRNA). In this work, we employed CyP, an LPS with TLR4-MD2 antagonist activity obtained from the cyanobacterium Oscillatoria planktothrix FP1, to study the effects on pro-inflammatory cytokine production and miRNA expression in human monocytic THP-1 cells stimulated with Pg-LPS or E. coli LPS (Ec-LPS). Results showed that CyP inhibited TNF-α, IL-1β and IL-8 expression more efficiently when co-incubated with Pg-LPS rather than with Ec-LPS. The inhibition of pro-inflammatory cytokine production was maintained even when CyP was added 2 h after LPS. The analysis of the effects of CyP on miRNA expression showed that, although being an antagonist, CyP did not inhibit miR-146a induced by Pg-LPS or Ec-LPS, whereas it significantly inhibited miR-155 only in the cultures stimulated with Ec-LPS. These results suggest that CyP may modulate the pro-inflammatory response induced by Pg-LPS, not only by blocking TLR4-MD2 complex, but also by preserving miR-146a expression. Full article
(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin)
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14 pages, 1481 KiB  
Article
Cyanobacteria Scytonema javanicum and Scytonema ocellatum Lipopolysaccharides Elicit Release of Superoxide Anion, Matrix-Metalloproteinase-9, Cytokines and Chemokines by Rat Microglia In Vitro
by Lucas C. Klemm, Evan Czerwonka, Mary L. Hall, Philip G. Williams and Alejandro M. S. Mayer
Toxins 2018, 10(4), 130; https://doi.org/10.3390/toxins10040130 - 21 Mar 2018
Cited by 7 | Viewed by 4383
Abstract
Cosmopolitan Gram-negative cyanobacteria may affect human and animal health by contaminating terrestrial, marine and freshwater environments with toxins, such as lipopolysaccharide (LPS). The cyanobacterial genus Scytonema (S) produces several toxins, but to our knowledge the bioactivity of genus Scytonema LPS has [...] Read more.
Cosmopolitan Gram-negative cyanobacteria may affect human and animal health by contaminating terrestrial, marine and freshwater environments with toxins, such as lipopolysaccharide (LPS). The cyanobacterial genus Scytonema (S) produces several toxins, but to our knowledge the bioactivity of genus Scytonema LPS has not been investigated. We recently reported that cyanobacterium Oscillatoria sp. LPS elicited classical and alternative activation of rat microglia in vitro. Thus, we hypothesized that treatment of brain microglia in vitro with either cyanobacteria S. javanicum or S. ocellatum LPS might stimulate classical and alternative activation with concomitant release of superoxide anion (O2−), matrix metalloproteinase-9 (MMP-9), cytokines and chemokines. Microglia were isolated from neonatal rats and treated in vitro with either S. javanicum LPS, S. ocellatum LPS, or E. coli LPS (positive control), in a concentration-dependent manner, for 18 h at 35.9 °C. We observed that treatment of microglia with either E. coli LPS, S. javanicum or S. ocellatum LPS generated statistically significant and concentration-dependent O2−, MMP-9 and pro-inflammatory cytokines IL-6 and TNF-α, pro-inflammatory chemokines MIP-2/CXCL-2, CINC-1/CXCL-1 and MIP-1α/CCL3, and the anti-inflammatory cytokine IL-10. Thus, our results provide experimental support for our working hypothesis because both S. javanicum and S. ocellatum LPS elicited classical and alternative activation of microglia and concomitant release of O2−, MMP-9, cytokines and chemokines in a concentration-dependent manner in vitro. To our knowledge this is the first report on the toxicity of cyanobacteria S. javanicum and S. ocellatum LPS to microglia, an immune cell type involved in neuroinflammation and neurotoxicity in the central nervous system. Full article
(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin)
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Review

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10 pages, 1329 KiB  
Review
Lipopolysaccharide Structural Differences between Western and Asian Helicobacter pylori Strains
by Hong Li, Hong Tang, Aleksandra W. Debowski, Keith A. Stubbs, Barry J. Marshall and Mohammed Benghezal
Toxins 2018, 10(9), 364; https://doi.org/10.3390/toxins10090364 - 08 Sep 2018
Cited by 10 | Viewed by 4761
Abstract
Recent structural analysis of the lipopolysaccharide (LPS) isolated from Helicobacter pylori G27 wild-type and O-antigen ligase mutant resulted in the redefinition of the core-oligosaccharide and O-antigen domains. The short core-oligosaccharide (Glc–Gal–Hep-III–Hep-II–Hep-I–KDO) and its attached trisaccharide (Trio, GlcNAc–Fuc–Hep) appear to be highly [...] Read more.
Recent structural analysis of the lipopolysaccharide (LPS) isolated from Helicobacter pylori G27 wild-type and O-antigen ligase mutant resulted in the redefinition of the core-oligosaccharide and O-antigen domains. The short core-oligosaccharide (Glc–Gal–Hep-III–Hep-II–Hep-I–KDO) and its attached trisaccharide (Trio, GlcNAc–Fuc–Hep) appear to be highly conserved structures among H. pylori strains. The G27 LPS contains a linear glucan–heptan linker between the core-Trio and distal Lewis antigens. This linker domain was commonly identified in Western strains. In contrast, out of 12 partial LPS structures of Asian strains, none displayed the heptan moiety, despite the presence of Lewis antigens. This raises the question of how Lewis antigens are attached to the Trio, and whether the LPS structure of Asian strains contain another linker. Of note, a riban was identified as a linker in LPS of the mouse-adapted SS1 strain, suggesting that alternative linker structures can occur. In summary, additional full structural analyses of LPS in Asian strains are required to assess the presence or absence of an alternative linker in these strains. It will also be interesting to study the glucan-heptan linker moieties in pathogenesis as H. pylori infections in Asia are usually more symptomatic than the ones presented in the Western world. Full article
(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin)
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9 pages, 1031 KiB  
Review
Endotoxins from a Pharmacopoeial Point of View
by Elvira Franco, Verónica Garcia-Recio, Pilar Jiménez, Manuel Garrosa, Tomás Girbés, Manuel Cordoba-Diaz and Damián Cordoba-Diaz
Toxins 2018, 10(8), 331; https://doi.org/10.3390/toxins10080331 - 16 Aug 2018
Cited by 23 | Viewed by 9213
Abstract
A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicity—that is, the [...] Read more.
A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicity—that is, the bacterial endotoxin test, and the pyrogen test. The main objective of this review is to compare the monographs of each test among the different Pharmacopeias, to detect similarities and differences. The former can be considered fully harmonized, and only non-significant differences were detected. The latter, which is the only available assay for some products and formulations to demonstrate apyrogenicity, shows large differences, which should be considered. Full article
(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin)
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19 pages, 6201 KiB  
Review
TRP Channels as Sensors of Bacterial Endotoxins
by Brett Boonen, Yeranddy A. Alpizar, Victor M. Meseguer and Karel Talavera
Toxins 2018, 10(8), 326; https://doi.org/10.3390/toxins10080326 - 11 Aug 2018
Cited by 42 | Viewed by 8181
Abstract
The cellular and systemic effects induced by bacterial lipopolysaccharides (LPS) have been solely attributed to the activation of the Toll-like receptor 4 (TLR4) signalling cascade. However, recent studies have shown that LPS activates several members of the Transient Receptor Potential (TRP) family of [...] Read more.
The cellular and systemic effects induced by bacterial lipopolysaccharides (LPS) have been solely attributed to the activation of the Toll-like receptor 4 (TLR4) signalling cascade. However, recent studies have shown that LPS activates several members of the Transient Receptor Potential (TRP) family of cation channels. Indeed, LPS induces activation of the broadly-tuned chemosensor TRPA1 in sensory neurons in a TLR4-independent manner, and genetic ablation of this channel reduced mouse pain and inflammatory responses triggered by LPS and the gustatory-mediated avoidance to LPS in fruit flies. LPS was also shown to activate TRPV4 channels in airway epithelial cells, an effect leading to an immediate production of bactericidal nitric oxide and to an increase in ciliary beat frequency. In this review, we discuss the role of TRP channels as sensors of bacterial endotoxins, and therefore, as crucial players in the timely detection of invading gram-negative bacteria. Full article
(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin)
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