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Lipopolysaccharide: Bacterial Endotoxin 2023

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

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 11883

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Prof. Dr. Susana Merino Montero

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

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Dear Colleagues,

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 highly 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 the 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 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, composition, biological activity, host interaction, and induction of the innate immunity of the Gram-negative bacterial endotoxin.

Prof. Dr. Susana Merino Montero
Guest Editor

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Keywords

lipid A
core LPS
O-antigen LPS
glycoconjugates
chemical structure
biological significance
host interaction
immune evasion

Published Papers (6 papers)

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Research

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14 pages, 2861 KiB

Open AccessArticle

Antigenic and Structural Properties of the Lipopolysaccharide of the Uropathogenic Proteus mirabilis Dm55 Strain Classified to a New O85 Proteus Serogroup

by Agata Palusiak, Anna Turska-Szewczuk and Dominika Drzewiecka

Int. J. Mol. Sci. 2023, 24(22), 16424; https://doi.org/10.3390/ijms242216424 - 16 Nov 2023

Viewed by 756

Abstract

The aim of the study was the serological and structural characterization of the lipopolysaccharide (LPS) O antigen from P. mirabilis Dm55 coming from the urine of a patient from Lodz. The Dm55 LPS was recognized in ELISA only by the O54 antiserum, suggesting a serological distinction of the Dm55 O antigen from all the 84 Proteus LPS serotypes described. The obtained polyclonal rabbit serum against P. mirabilis Dm55 reacted in ELISA and Western blotting with a few LPSs (including O54), but the reactions were weaker than those observed in the homologous system. The LPS of P. mirabilis Dm55 was subjected to mild acid hydrolysis, and the obtained high-molecular-mass O polysaccharide was chemically studied using sugar and methylation analyses, mass spectrometry, and ¹H and ¹³C NMR spectroscopy, including ¹H,¹H NOESY, and ¹H,¹³C HMBC experiments. The Dm55 O unit is a branched three-saccharide, and its linear fragment contains α-GalpNAc and β-Galp, whereas α-GlcpNAc occupies a terminal position. The Dm55 OPS shares a disaccharide epitope with the Proteus O54 antigen. Due to the structural differences of the studied O antigen from the other described Proteus O polysaccharides, we propose to classify the P. mirabilis Dm55 strain to a new Proteus O85 serogroup. Full article

(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin 2023)

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17 pages, 6742 KiB

Open AccessArticle

Structural Diversity among Edwardsiellaceae Core Oligosaccharides

by Maria Jordán, Sylwia Wojtys-Tekiel, Susana Merino, Juan M. Tomás and Marta Kaszowska

Int. J. Mol. Sci. 2023, 24(5), 4768; https://doi.org/10.3390/ijms24054768 - 01 Mar 2023

Viewed by 1260

Abstract

The Edwardsiella genus presents five different pathogenic species: Edwardsiella tarda, E. anguillarum, E. piscicida, E. hoshinae and E. ictaluri. These species cause infections mainly in fish, but they can also infect reptiles, birds or humans. Lipopolysaccharide (endotoxin) plays an important role in the pathogenesis of these bacteria. For the first time, the chemical structure and genomics of the lipopolysaccharide (LPS) core oligosaccharides of E. piscicida, E. anguillarum, E. hoshinae and E. ictaluri were studied. The complete gene assignments for all core biosynthesis gene functions were acquired. The structure of core oligosaccharides was investigated by ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy. The structures of E. piscicida and E. anguillarum core oligosaccharides show the presence of →3,4)-L-glycero-α-D-manno-Hepp, two terminal β-D-Glcp, →2,3,7)-L-glycero-α-D-manno-Hepp, →7)-L-glycero-α-D-manno-Hepp, terminal α-D-GlcpN, two →4)-α-D-GalpA, → 3)-α-D-GlcpNAc, terminal β-D-Galp and →5-substituted Kdo. E. hoshinare core oligosaccharide shows only one terminal β-D-Glcp, and instead of terminal β-D-Galp a terminal α-D-GlcpNAc. E. ictaluri core oligosaccharide shows only one terminal β-D-Glcp, one →4)-α-D-GalpA and do not have terminal α-D-GlcpN (see complementary figure). Full article

(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin 2023)

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17 pages, 2660 KiB

Open AccessArticle

Protective Effect of Nopal Cactus (Opuntia ficus-indica) Seed Oil against Short-Term Lipopolysaccharides-Induced Inflammation and Peroxisomal Functions Dysregulation in Mouse Brain and Liver

by Mounia Tahri-Joutey, Fatima-Ezzahra Saih, Riad El Kebbaj, Catherine Gondcaille, Joseph Vamecq, Norbert Latruffe, Gérard Lizard, Stéphane Savary, Boubker Nasser, Mustapha Cherkaoui-Malki and Pierre Andreoletti

Int. J. Mol. Sci. 2022, 23(19), 11849; https://doi.org/10.3390/ijms231911849 - 06 Oct 2022

Cited by 3 | Viewed by 1662

Abstract

Exposure to endotoxins (lipopolysaccharides, LPS) may lead to a potent inflammatory cytokine response and a severe impairment of metabolism, causing tissue injury. The protective effect provided by cactus seed oil (CSO), from Opuntia ficus-indica, was evaluated against LPS-induced inflammation, dysregulation of peroxisomal antioxidant, and β-oxidation activities in the brain and the liver. In both tissues, a short-term LPS exposure increased the proinflammatory interleukine-1β (Il-1β), inducible Nitroxide synthase (iNos), and Interleukine-6 (Il-6). In the brain, CSO action reduced only LPS-induced iNos expression, while in the liver, CSO attenuated mainly the hepatic Il-1β and Il-6. Regarding the peroxisomal antioxidative functions, CSO treatment (as Olive oil (OO) or Colza oil (CO) treatment) induced the hepatic peroxisomal Cat gene. Paradoxically, we showed that CSO, as well as OO or CO, treatment can timely induce catalase activity or prevent its induction by LPS, respectively, in both brain and liver tissues. On the other hand, CSO (as CO) pretreatment prevented the LPS-associated Acox1 gene and activity decreases in the liver. Collectively, CSO showed efficient neuroprotective and hepato-protective effects against LPS, by maintaining the brain peroxisomal antioxidant enzyme activities of catalase and glutathione peroxidase, and by restoring hepatic peroxisomal antioxidant and β-oxidative capacities. Full article

(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin 2023)

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14 pages, 2089 KiB

Open AccessArticle

The Anti-Inflammatory Effect of Carrageenan/Echinochrom Complex at Experimental Endotoxemia

by Irina M. Yermak, Anna O. Kravchenko, Eleonora I. Khasina, Ekaterina S. Menchinskaya, Evgeny A. Pislyagin, Ekaterina V. Sokolova, Galina N. Likhatskaya and Dmitry L. Aminin

Int. J. Mol. Sci. 2022, 23(19), 11702; https://doi.org/10.3390/ijms231911702 - 03 Oct 2022

Cited by 2 | Viewed by 1429

Abstract

The anti-inflammatory effects of the CRG/Ech complex in LPS-induced endotoxemia were investigated in vivo in mice and in vitro in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The results indicated that the CRG/Ech complex suppressed the LPS-induced inflammatory response by reducing the production of ROS and NO in the macrophages. Furthermore, the in vivo experiment indicated that the CRG/Ech complex minimized disorders of the physiological and metabolic processes in mice subjected to LPS intoxication and reduced the levels of proinflammatory cytokines in the mouse serum. The preventive administration of the CRG/Ech complex to mice prevented endotoxin-induced damage in the mouse model of endotoxemia, increased the mice’s resistance to LPS, and prevented increases in the levels of proinflammatory cytokines (TNFα). In this work, we showed by the molecular docking that Ech interacted with carrageenan, and that H-donor and H-acceptor bonds are involved in the formation of the complex. Full article

(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin 2023)

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Review

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16 pages, 967 KiB

Open AccessReview

A Comparison between SARS-CoV-2 and Gram-Negative Bacteria-Induced Hyperinflammation and Sepsis

by Klaus Brandenburg, Raquel Ferrer-Espada, Guillermo Martinez-de-Tejada, Christian Nehls, Satoshi Fukuoka, Karl Mauss, Günther Weindl and Patrick Garidel

Int. J. Mol. Sci. 2023, 24(20), 15169; https://doi.org/10.3390/ijms242015169 - 14 Oct 2023

Cited by 1 | Viewed by 1580

Abstract

Sepsis is a life-threatening condition caused by the body’s overwhelming response to an infection, such as pneumonia or urinary tract infection. It occurs when the immune system releases cytokines into the bloodstream, triggering widespread inflammation. If not treated, it can lead to organ failure and death. Unfortunately, sepsis has a high mortality rate, with studies reporting rates ranging from 20% to over 50%, depending on the severity and promptness of treatment. According to the World Health Organization (WHO), the annual death toll in the world is about 11 million. One of the main toxins responsible for inflammation induction are lipopolysaccharides (LPS, endotoxin) from Gram-negative bacteria, which rank among the most potent immunostimulants found in nature. Antibiotics are consistently prescribed as a part of anti-sepsis-therapy. However, antibiotic therapy (i) is increasingly ineffective due to resistance development and (ii) most antibiotics are unable to bind and neutralize LPS, a prerequisite to inhibit the interaction of endotoxin with its cellular receptor complex, namely Toll-like receptor 4 (TLR4)/MD-2, responsible for the intracellular cascade leading to pro-inflammatory cytokine secretion. The pandemic virus SARS-CoV-2 has infected hundreds of millions of humans worldwide since its emergence in 2019. The COVID-19 (Coronavirus disease-19) caused by this virus is associated with high lethality, particularly for elderly and immunocompromised people. As of August 2023, nearly 7 million deaths were reported worldwide due to this disease. According to some reported studies, upregulation of TLR4 and the subsequent inflammatory signaling detected in COVID-19 patients “mimics bacterial sepsis”. Furthermore, the immune response to SARS-CoV-2 was described by others as “mirror image of sepsis”. Similarly, the cytokine profile in sera from severe COVID-19 patients was very similar to those suffering from the acute respiratory distress syndrome (ARDS) and sepsis. Finally, the severe COVID-19 infection is frequently accompanied by bacterial co-infections, as well as by the presence of significant LPS concentrations. In the present review, we will analyze similarities and differences between COVID-19 and sepsis at the pathophysiological, epidemiological, and molecular levels. Full article

(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin 2023)

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34 pages, 20227 KiB

Open AccessReview

Heterogeneity of Lipopolysaccharide as Source of Variability in Bioassays and LPS-Binding Proteins as Remedy

by Alexandra C. Fux, Cristiane Casonato Melo, Sara Michelini, Benjamin J. Swartzwelter, Andreas Neusch, Paola Italiani and Martin Himly

Int. J. Mol. Sci. 2023, 24(9), 8395; https://doi.org/10.3390/ijms24098395 - 07 May 2023

Cited by 15 | Viewed by 4016

Abstract

Lipopolysaccharide (LPS), also referred to as endotoxin, is the major component of Gram-negative bacteria’s outer cell wall. It is one of the main types of pathogen-associated molecular patterns (PAMPs) that are known to elicit severe immune reactions in the event of a pathogen trespassing the epithelial barrier and reaching the bloodstream. Associated symptoms include fever and septic shock, which in severe cases, might even lead to death. Thus, the detection of LPS in medical devices and injectable pharmaceuticals is of utmost importance. However, the term LPS does not describe one single molecule but a diverse class of molecules sharing one common feature: their characteristic chemical structure. Each bacterial species has its own pool of LPS molecules varying in their chemical composition and enabling the aggregation into different supramolecular structures upon release from the bacterial cell wall. As this heterogeneity has consequences for bioassays, we aim to examine the great variability of LPS molecules and their potential to form various supramolecular structures. Furthermore, we describe current LPS quantification methods and the LPS-dependent inflammatory pathway and show how LPS heterogeneity can affect them. With the intent of overcoming these challenges and moving towards a universal approach for targeting LPS, we review current studies concerning LPS-specific binders. Finally, we give perspectives for LPS research and the use of LPS-binding molecules. Full article

(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin 2023)

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Lipopolysaccharide: Bacterial Endotoxin 2023

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