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Special Issue "Marine Lipopolysaccharides"

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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (30 April 2015)

Special Issue Editor

Guest Editor
Prof. Dr. Antonio Molinaro

Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte Santangelo, Via Cintia 4, I-80126 Napoli, Italy
E-Mail
Fax: +39 081 674 393
Interests: carbohydrates; lipopolysaccharides; polysaccharides; innate immunity; glycoconjugates; NMR

Special Issue Information

Dear Colleagues,

Marine bacteria are microorganisms that have adapted, through millions of years, to the survival in environments often characterized by one or more physico-chemical extreme parameters, such as pressure, temperature and salinity. The main interest in the research about marine bacteria is due to their ability to produce several biologically active molecules, such as antibiotics, toxins and antitoxins, antitumor and antimicrobial agents.

Lipopolysaccharides, LPSs, composing about 75% of the outer membrane of Gram negative bacteria and exposed toward the external environment, play an essential role in the adaptation of the organisms to the peculiar external surroundings. The study of LPS primary structure and the (supra)molecular architecture of such molecules is related to the possibility of thriving in marine habitats, shielding the cell from the disrupting action of natural stress factors.

LPSs are build up according to a common structural architecture and are composed of a hydrophilic hetero-polysaccharide (formed by core oligosaccharide and O-specific polysaccharide or O-chain) covalently linked to a lipophilic moiety termed lipid A, which is embedded in the outer leaflet and anchors these macromolecules to the membrane through electrostatic and hydrophobic interactions. LPSs not containing O-chain are termed Rough (R-) LPSs or lipooligosaccharides (LOSs). LOSs may occur in both wild and laboratory strains possessing mutations in the genes encoding the O-specific polysaccharide biosynthesis or transfer. Lipid A possesses a rather conservative structure consisting of α-(1→6)-glucosamine disaccharide backbone phosphorylated at positions 1 and 4’ and acylated with primary 3-hydroxy fatty acids at positions 2 and 3 of both GlcN residues; the hydroxyl groups of the primary fatty acids can be further acylated by secondary acyl moieties. In the core oligosaccharide an inner and outer region are usually distinguished: the inner core, proximal to the lipid A, consists of typical monose residues as Kdo (3-deoxy-D-manno-ocutolonic acid) and heptoses, often carrying negatively charged groups. Kdo is attached to the GlcN II of lipid A backbone and is the first sugar of the core oligosaccharide. The outer core region is more variable and is usually composed by hexoses. The LPS adaptive and dynamic changes managed by Gram-negative bacteria act on the carbohydrate backbone, on the polar heads and the acyl chain composition, and show the primary protective role that the LPSs operate in bacteria.

Another main reason to study LPS structure from marine bacteria is that the LPS lipid A is the primary immuno-stimulator centre of Gram negative bacteria, it triggers the activation of the innate immune system of eukaryotics (both animals and plants) through the interaction with particular proteins called pathogen related receptors, such as the toll like receptors in mammals. The toxicity of the lipid A is depending on its primary structure. The study of lipid A structures from non-toxic Gram-negative bacteria is extremely important in order to identify lipid A analogues which can antagonise the biological activation of competent mammalian host-cells by lipid A. Within this frame, lipopolysaccharides (LPSs), or their portions, from marine bacteria, have often shown low virulence, and represent potential candidates in the development of drugs to prevent septic shock.

The primary and secondary structure of a lipopolysaccharide is attained by a combinatiuon of chemical and biochemical techniques and state-of-art MS spectrometry and NMR spectroscopy.

Prof. Dr. Antonio Molinaro
Guest Editor

Submission

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Keywords

  • endotoxin
  • lipopolysaccharide
  • lipid A
  • O-polysaccharide
  • marine bacteria
  • glycoconjugates
  • NMR spectroscopy
  • mass spectrometry

Published Papers (18 papers)

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Research

Jump to: Review, Other

Open AccessArticle Lipopolysaccharides from Commensal and Opportunistic Bacteria: Characterization and Response of the Immune System of the Host Sponge Suberites domuncula
Mar. Drugs 2015, 13(8), 4985-5006; doi:10.3390/md13084985
Received: 30 April 2015 / Revised: 17 July 2015 / Accepted: 20 July 2015 / Published: 7 August 2015
Cited by 3 | PDF Full-text (549 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Marine sponges harbor a rich bacterioflora with which they maintain close relationships. However, the way these animals make the distinction between bacteria which are consumed to meet their metabolic needs and opportunistic and commensal bacteria which are hosted is not elucidated. Among the
[...] Read more.
Marine sponges harbor a rich bacterioflora with which they maintain close relationships. However, the way these animals make the distinction between bacteria which are consumed to meet their metabolic needs and opportunistic and commensal bacteria which are hosted is not elucidated. Among the elements participating in this discrimination, bacterial cell wall components such as lipopolysaccharides (LPS) could play a role. In the present study, we investigated the LPS chemical structure of two bacteria associated with the sponge Suberites domuncula: a commensal Endozoicomonas sp. and an opportunistic Pseudoalteromonas sp. Electrophoretic patterns indicated different LPS structures for these bacteria. The immunomodulatory lipid A was isolated after mild acetic acid hydrolysis. The electrospray ionization ion-trap mass spectra revealed monophosphorylated molecules corresponding to tetra- and pentaacylated structures with common structural features between the two strains. Despite peculiar structural characteristics, none of these two LPS influenced the expression of the macrophage-expressed gene S. domuncula unlike the Escherichia coli ones. Further research will have to include a larger number of genes to understand how this animal can distinguish between LPS with resembling structures and discriminate between bacteria associated with it. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessArticle Temperature-Dependence of Lipid A Acyl Structure in Psychrobacter cryohalolentis and Arctic Isolates of Colwellia hornerae and Colwellia piezophila
Mar. Drugs 2015, 13(8), 4701-4720; doi:10.3390/md13084701
Received: 1 May 2015 / Revised: 19 July 2015 / Accepted: 20 July 2015 / Published: 30 July 2015
PDF Full-text (927 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lipid A is a fundamental Gram-negative outer membrane component and the essential element of lipopolysaccharide (endotoxin), a potent immunostimulatory molecule. This work describes the metabolic adaptation of the lipid A acyl structure by Psychrobacter cryohalolentis at various temperatures in its facultative psychrophilic growth
[...] Read more.
Lipid A is a fundamental Gram-negative outer membrane component and the essential element of lipopolysaccharide (endotoxin), a potent immunostimulatory molecule. This work describes the metabolic adaptation of the lipid A acyl structure by Psychrobacter cryohalolentis at various temperatures in its facultative psychrophilic growth range, as characterized by MALDI-TOF MS and FAME GC-MS. It also presents the first elucidation of lipid A structure from the Colwellia genus, describing lipid A from strains of Colwellia hornerae and Colwellia piezophila, which were isolated as primary cultures from Arctic fast sea ice and identified by 16S rDNA sequencing. The Colwellia strains are obligate psychrophiles, with a growth range restricted to 15 °C or less. As such, these organisms have less need for fluidity adaptation in the acyl moiety of the outer membrane, and they do not display alterations in lipid A based on growth temperature. Both Psychrobacter and Colwellia make use of extensive single-methylene variation in the size of their lipid A molecules. Such single-carbon variations in acyl size were thought to be restricted to psychrotolerant (facultative) species, but its presence in these Colwellia species shows that odd-chain acyl units and a single-carbon variation in lipid A structure are present in obligate psychrophiles, as well. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
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Open AccessArticle Functional Genomics of the Aeromonas salmonicida Lipopolysaccharide O-Antigen and A-Layer from Typical and Atypical Strains
Mar. Drugs 2015, 13(6), 3791-3808; doi:10.3390/md13063791
Received: 14 April 2015 / Accepted: 27 April 2015 / Published: 15 June 2015
Cited by 2 | PDF Full-text (1082 KB) | HTML Full-text | XML Full-text
Abstract
The A. salmonicida A450 LPS O-antigen, encoded by the wbsalmo gene cluster, is exported through an ABC-2 transporter-dependent pathway. It represents the first example of an O-antigen LPS polysaccharide with three different monosaccharides in their repeating unit assembled by this pathway. Until
[...] Read more.
The A. salmonicida A450 LPS O-antigen, encoded by the wbsalmo gene cluster, is exported through an ABC-2 transporter-dependent pathway. It represents the first example of an O-antigen LPS polysaccharide with three different monosaccharides in their repeating unit assembled by this pathway. Until now, only repeating units with one or two different monosaccharides have been described. Functional genomic analysis of this wbsalmo region is mostly in agreement with the LPS O-antigen structure of acetylated l-rhamnose (Rha), d-glucose (Glc), and 2-amino-2-deoxy-d-mannose (ManN). Between genes of the wbsalmo we found the genes responsible for the biosynthesis and assembly of the S-layer (named A-layer in these strains). Through comparative genomic analysis and in-frame deletions of some of the genes, we concluded that all the A. salmonicida typical and atypical strains, other than A. salmonicida subsp. pectinolytica strains, shared the same wbsalmo and presence of A-layer. A. salmonicida subsp. pectinolytica strains lack wbsalmo and A-layer, two major virulence factors, and this could be the reason they are the only ones not found as fish pathogens. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
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Open AccessArticle Influence of Core Oligosaccharide of Lipopolysaccharide to Outer Membrane Behavior of Escherichia coli
Mar. Drugs 2015, 13(6), 3325-3339; doi:10.3390/md13063325
Received: 14 April 2015 / Revised: 10 May 2015 / Accepted: 19 May 2015 / Published: 27 May 2015
Cited by 6 | PDF Full-text (1167 KB) | HTML Full-text | XML Full-text
Abstract
Lipopolysaccharides, major molecules in the outer membrane of Gram-negative bacteria, play important roles on membrane integrity of the cell. However, how the core oligosaccharide of lipopolysaccharide affect the membrane behavior is not well understood. In this study, the relationship between the core oligosaccharide
[...] Read more.
Lipopolysaccharides, major molecules in the outer membrane of Gram-negative bacteria, play important roles on membrane integrity of the cell. However, how the core oligosaccharide of lipopolysaccharide affect the membrane behavior is not well understood. In this study, the relationship between the core oligosaccharide of lipopolysaccharide and the membrane behavior was investigated using a series of Escherichia coli mutants defective in genes to affect the biosynthesis of core oligosaccharide of lipopolysaccharide. Cell surface hydrophobicity, outer membrane permeability, biofilm formation and auto-aggregation of these mutant cells were compared. Compared to the wild type W3110, cell surface hydrophobicities of mutant ΔwaaC, ΔwaaF, ΔwaaG, ΔwaaO, ΔwaaP, ΔwaaY and ΔwaaB were enhanced, outer membrane permeabilities of ΔwaaC, ΔwaaF, ΔwaaG and ΔwaaP were significantly increased, abilities of biofilm formation by ΔwaaC, ΔwaaF, ΔwaaG, ΔwaaO, ΔwaaR, ΔwaaP, ΔwaaQ and ΔwaaY decreased, and auto-aggregation abilities of ΔwaaC, ΔwaaF, ΔwaaG, ΔwaaO, ΔwaaR, ΔwaaU, ΔwaaP and ΔwaaY were strongly enhanced. These results give new insight into the influence of core oligosaccharide of lipopolysaccharide on bacterial cell membrane behavior. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessArticle Construction of Escherichia coli Mutant with Decreased Endotoxic Activity by Modifying Lipid A Structure
Mar. Drugs 2015, 13(6), 3388-3406; doi:10.3390/md13063388
Received: 31 March 2015 / Revised: 18 May 2015 / Accepted: 19 May 2015 / Published: 27 May 2015
PDF Full-text (1349 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Escherichia coli BL21 (DE3) and its derivatives are widely used for the production of recombinant proteins, but these purified proteins are always contaminated with lipopolysaccharide (LPS). LPS is recognized by the toll-like receptor 4 and myeloid differentiation factor 2 complex of mammalian immune
[...] Read more.
Escherichia coli BL21 (DE3) and its derivatives are widely used for the production of recombinant proteins, but these purified proteins are always contaminated with lipopolysaccharide (LPS). LPS is recognized by the toll-like receptor 4 and myeloid differentiation factor 2 complex of mammalian immune cells and leads to release of pro-inflammatory cytokines. It is a vital step to remove LPS from the proteins before use for therapeutic purpose. In this study, we constructed BL21 (DE3) ∆msbB28 pagP38 mutant, which produces a penta-acylated LPS with reduced endotoxicity. The plasmids harboring pagL and/or lpxE were then introduced into this mutant to further modify the LPS. The new strain (S004) carrying plasmid pQK004 (pagL and lpxE) produced mono-phosphoryated tetra-acylated lipid A, which induces markedly less production of tumor necrosis factor-α in the RAW264.7 and IL-12 in the THP1, but still retains ability to produce recombinant proteins. This study provides a strategy to decrease endotoxic activity of recombinant proteins purified from E. coli BL21 backgrounds and a feasible approach to modify lipid A structure for alternative purposes such as mono-phosphoryl lipid A (MPL) as vaccine adjuvants. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessArticle Molecular and Chemical Analysis of the Lipopolysaccharide from Aeromonas hydrophila Strain AH-1 (Serotype O11)
Mar. Drugs 2015, 13(4), 2233-2249; doi:10.3390/md13042233
Received: 27 February 2015 / Revised: 30 March 2015 / Accepted: 7 April 2015 / Published: 14 April 2015
Cited by 4 | PDF Full-text (739 KB) | HTML Full-text | XML Full-text
Abstract
A group of virulent Aeromonas hydrophila, A. sobria, and A. veronii biovar sobria strains isolated from humans and fish have been described; these strains classified to serotype O11 are serologically related by their lipopolysaccharide (LPS) O-antigen (O-polysaccharide), and
[...] Read more.
A group of virulent Aeromonas hydrophila, A. sobria, and A. veronii biovar sobria strains isolated from humans and fish have been described; these strains classified to serotype O11 are serologically related by their lipopolysaccharide (LPS) O-antigen (O-polysaccharide), and the presence of an S-layer consisting of multiple copies of a crystalline surface array protein with a molecular weight of 52 kDa in the form of a crystalline surface array which lies peripheral to the cell wall. A. hydrophila strain AH-1 is one of them. We isolated the LPS from this strain and determined the structure of the O-polysaccharide, which was similar to that previously described for another strain of serotype O11. The genetics of the O11-antigen showed the genes (wbO11 cluster) in two sections separated by genes involved in biosynthesis and assembly of the S-layer. The O11-antigen LPS is an example of an ABC-2-transporter-dependent pathway for O-antigen heteropolysaccharide (disaccharide) assembly. The genes involved in the biosynthesis of the LPS core (waaO11 cluster) were also identified in three different chromosome regions being nearly identical to the ones described for A. hydrophila AH-3 (serotype O34). The genetic data and preliminary chemical analysis indicated that the LPS core for strain AH-1 is identical to the one for strain AH-3. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
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Open AccessArticle Vibrio vulnificus MO6-24/O Lipopolysaccharide Stimulates Superoxide Anion, Thromboxane B2, Matrix Metalloproteinase-9, Cytokine and Chemokine Release by Rat Brain Microglia in Vitro
Mar. Drugs 2014, 12(4), 1732-1756; doi:10.3390/md12041732
Received: 28 December 2013 / Revised: 26 February 2014 / Accepted: 26 February 2014 / Published: 26 March 2014
Cited by 2 | PDF Full-text (785 KB) | HTML Full-text | XML Full-text
Abstract
Although human exposure to Gram-negative Vibrio vulnificus (V. vulnificus) lipopolysaccharide (LPS) has been reported to result in septic shock, its impact on the central nervous system’s innate immunity remains undetermined. The purpose of this study was to determine whether V. vulnificus
[...] Read more.
Although human exposure to Gram-negative Vibrio vulnificus (V. vulnificus) lipopolysaccharide (LPS) has been reported to result in septic shock, its impact on the central nervous system’s innate immunity remains undetermined. The purpose of this study was to determine whether V. vulnificus MO6-24/O LPS might activate rat microglia in vitro and stimulate the release of superoxide anion (O2), a reactive oxygen species known to cause oxidative stress and neuronal injury in vivo. Brain microglia were isolated from neonatal rats, and then treated with either V. vulnificus MO6-24/O LPS or Escherichia coli O26:B6 LPS for 17 hours in vitro. O2 was determined by cytochrome C reduction, and matrix metalloproteinase-2 (MMP-2) and MMP-9 by gelatinase zymography. Generation of cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 alpha (IL-1α), IL-6, and transforming growth factor-beta 1 (TGF-β1), chemokines macrophage inflammatory protein (MIP-1α)/chemokine (C-C motif) ligand 3 (CCL3), MIP-2/chemokine (C-X-C motif) ligand 2 (CXCL2), monocyte chemotactic protein-1 (MCP-1)/CCL2, and cytokine-induced neutrophil chemoattractant-2alpha/beta (CINC-2α/β)/CXCL3, and brain-derived neurotrophic factor (BDNF), were determined by specific immunoassays. Priming of rat microglia by V. vulnificus MO6-24/O LPS in vitro yielded a bell-shaped dose-response curve for PMA (phorbol 12-myristate 13-acetate)-stimulated O2 generation: (1) 0.1–1 ng/mL V. vulnificus LPS enhanced O2 generation significantly but with limited inflammatory mediator generation; (2) 10–100 ng/mL V. vulnificus LPS maximized O2 generation with concomitant release of thromboxane B2 (TXB2), matrix metalloproteinase-9 (MMP-9), and several cytokines and chemokines; (3) 1000–100,000 ng/mL V. vulnificus LPS, with the exception of TXB2, yielded both attenuated O2 production, and a progressive decrease in MMP-9, cytokines and chemokines investigated. Thus concentration-dependent treatment of neonatal brain microglia with V. vulnificus MO6-24/O LPS resulted in a significant rise in O2 production, followed by a progressive decrease in O2 release, with concomitant release of lactic dehydrogenase (LDH), and generation of TXB2, MMP-9, cytokines and chemokines. We hypothesize that the inflammatory mediators investigated may be cytotoxic to microglia in vitro, by an as yet undetermined autocrine mechanism. Although V. vulnificus LPS was less potent than E. coli LPS in vitro, inflammatory mediator release by the former was clearly more efficacious. Finally, we hypothesize that should V. vulnificus LPS gain entry into the CNS, it would be possible that microglia might become activated, resulting in high levels of O2 as well as neuroinflammatory TXB2, MMP-9, cytokines and chemokines. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessArticle Construction and Characterization of an Escherichia coli Mutant Producing Kdo2-Lipid A
Mar. Drugs 2014, 12(3), 1495-1511; doi:10.3390/md12031495
Received: 8 December 2013 / Revised: 6 February 2014 / Accepted: 13 February 2014 / Published: 13 March 2014
Cited by 5 | PDF Full-text (1136 KB) | HTML Full-text | XML Full-text
Abstract
3-deoxy-d-manno-oct-2-ulosonic acid (Kdo)2-lipid A is the conserved structure domain of lipopolysaccharide found in most Gram-negative bacteria, and it is believed to stimulate the innate immune system through the TLR4/MD2 complex. Therefore, Kdo2-lipid A is an important stimulator
[...] Read more.
3-deoxy-d-manno-oct-2-ulosonic acid (Kdo)2-lipid A is the conserved structure domain of lipopolysaccharide found in most Gram-negative bacteria, and it is believed to stimulate the innate immune system through the TLR4/MD2 complex. Therefore, Kdo2-lipid A is an important stimulator for studying the mechanism of the innate immune system and for developing bacterial vaccine adjuvants. Kdo2-lipid A has not been chemically synthesized to date and could only be isolated from an Escherichia coli mutant strain, WBB06. WBB06 cells grow slowly and have to grow in the presence of tetracycline. In this study, a novel E. coli mutant strain, WJW00, that could synthesize Kdo2-lipid A was constructed by deleting the rfaD gene from the genome of E. coli W3110. The rfaD gene encodes ADP-l-glycero-d-manno-heptose-6-epimerase RfaD. Based on the analysis by SDS-PAGE, thin layer chromatography (TLC) and electrospray ionization mass spectrometry (ESI/MS), WJW00 could produce similar levels of Kdo2-lipid A to WBB06. WJW00 cells grow much better than WBB06 cells and do not need to add any antibiotics during growth. Compared with the wild-type strain, W3110, WJW00 showed increased hydrophobicity, higher cell permeability, greater autoaggregation and decreased biofilm-forming ability. Therefore, WJW00 could be a more suitable strain than WBB06 for producing Kdo2-lipid A and a good base strain for developing lipid A adjuvants. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessArticle Structural Studies of the Lipopolysaccharide from the Fish Pathogen Aeromonas veronii Strain Bs19, Serotype O16
Mar. Drugs 2014, 12(3), 1298-1316; doi:10.3390/md12031298
Received: 24 December 2013 / Revised: 27 January 2014 / Accepted: 8 February 2014 / Published: 7 March 2014
Cited by 2 | PDF Full-text (1051 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Chemical analyses, mass spectrometry, and NMR spectroscopy were applied to study the structure of the lipopolysaccharide (LPS) isolated from Aeromonas veronii strain Bs19, serotype O16. ESI-MS revealed that the most abundant LPS glycoforms have tetra-acylated or hexa-acylated lipid A species, consisting of a
[...] Read more.
Chemical analyses, mass spectrometry, and NMR spectroscopy were applied to study the structure of the lipopolysaccharide (LPS) isolated from Aeromonas veronii strain Bs19, serotype O16. ESI-MS revealed that the most abundant LPS glycoforms have tetra-acylated or hexa-acylated lipid A species, consisting of a bisphosphorylated GlcN disaccharide with an AraN residue as a non-stoichiometric substituent, and a core oligosaccharide composed of Hep5Hex3HexN1Kdo1P1. Sugar and methylation analysis together with 1D and 2D 1H and 13C NMR spectroscopy were the main methods used, and revealed that the O-specific polysaccharide (OPS) of A. veronii Bs19 was built up of tetrasaccharide repeating units with the structure: →4)-α-d-Quip3NAc-(1→3)-α-l-Rhap-(1→4)-β-d-Galp-(1→3)-α-d-GalpNAc-(1→. This composition was confirmed by mass spectrometry. The charge-deconvoluted ESI FT-ICR MS recorded for the LPS preparations identified mass peaks of SR- and R-form LPS species, that differed by Δm = 698.27 u, a value corresponding to the calculated molecular mass of one OPS repeating unit (6dHexNAc6dHexHexHexNAc-H2O). Moreover, unspecific fragmentation spectra confirmed the sequence of the sugar residues in the OPS and allowed to assume that the elucidated structure also represented the biological repeating unit. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
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Open AccessArticle Influence of Lipid A Acylation Pattern on Membrane Permeability and Innate Immune Stimulation
Mar. Drugs 2013, 11(9), 3197-3208; doi:10.3390/md11093197
Received: 30 June 2013 / Revised: 29 July 2013 / Accepted: 9 August 2013 / Published: 26 August 2013
Cited by 6 | PDF Full-text (353 KB) | HTML Full-text | XML Full-text
Abstract
Lipid A, the hydrophobic anchor of lipopolysaccharide (LPS), is an essential component in the outer membrane of Gram-negative bacteria. It can stimulate the innate immune system via Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD2), leading to the release of inflammatory cytokines. In this
[...] Read more.
Lipid A, the hydrophobic anchor of lipopolysaccharide (LPS), is an essential component in the outer membrane of Gram-negative bacteria. It can stimulate the innate immune system via Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD2), leading to the release of inflammatory cytokines. In this study, six Escherichia coli strains which can produce lipid A with different acylation patterns were constructed; the influence of lipid A acylation pattern on the membrane permeability and innate immune stimulation has been systematically investigated. The lipid A species were isolated and identified by matrix assisted laser ionization desorption-time of flight/tandem mass spectrometry. N-Phenyl naphthylamine uptake assay and antibiotic susceptibility test showed that membrane permeability of these strains were different. The lower the number of acyl chains in lipid A, the stronger the membrane permeability. LPS purified from these strains were used to stimulate human or mouse macrophage cells, and different levels of cytokines were induced. Compared with wild type hexa-acylated LPS, penta-acylated, tetra-acylated and tri-acylated LPS induced lower levels of cytokines. These results suggest that the lipid A acylation pattern influences both the bacterial membrane permeability and innate immune stimulation. The results would be useful for redesigning the bacterial membrane structure and for developing lipid A vaccine adjuvant. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessArticle Structural and Immunochemical Studies of the Lipopolysaccharide from the Fish Pathogen, Aeromonas bestiarum Strain K296, Serotype O18
Mar. Drugs 2013, 11(4), 1235-1255; doi:10.3390/md11041235
Received: 25 February 2013 / Revised: 8 March 2013 / Accepted: 18 March 2013 / Published: 17 April 2013
Cited by 4 | PDF Full-text (922 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chemical analyses and mass spectrometry were used to study the structure of the lipopolysaccharide (LPS) isolated from Aeromonas bestiarum strain K296, serotype O18. ESI-MS revealed that the most abundant A. bestiarum LPS glycoforms have a hexa-acylated or tetra-acylated lipid A with conserved architecture
[...] Read more.
Chemical analyses and mass spectrometry were used to study the structure of the lipopolysaccharide (LPS) isolated from Aeromonas bestiarum strain K296, serotype O18. ESI-MS revealed that the most abundant A. bestiarum LPS glycoforms have a hexa-acylated or tetra-acylated lipid A with conserved architecture of the backbone, consisting of a 1,4′-bisphosphorylated β-(1→6)-linked d-GlcN disaccharide with an AraN residue as a non-stoichiometric substituent and a core oligosaccharide composed of Kdo1Hep6Hex1HexN1P1. 1D and 2D NMR spectroscopy revealed that the O-specific polysaccharide (OPS) of A. bestiarum K296 consists of a branched tetrasaccharide repeating unit containing two 6-deoxy-l-talose (6dTalp), one Manp and one GalpNAc residues; thus, it is similar to that of the OPS of A. hydrophila AH-3 (serotype O34) in both the sugar composition and the glycosylation pattern. Moreover, 3-substituted 6dTalp was 2-O-acetylated and additional O-acetyl groups were identified at O-2 and O-4 (or O-3) positions of the terminal 6dTalp. Western blots with polyclonal rabbit sera showed that serotypes O18 and O34 share some epitopes in the LPS. The very weak reaction of the anti-O34 serum with the O-deacylated LPS of A. bestiarum K296 might have been due to the different O-acetylation pattern of the terminal 6dTalp. The latter suggestion was further confirmed by NMR. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
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Open AccessArticle The Lipid A from the Haloalkaliphilic Bacterium Salinivibrio sharmensis Strain BAGT
Mar. Drugs 2013, 11(1), 184-193; doi:10.3390/md11010184
Received: 11 December 2012 / Revised: 9 January 2013 / Accepted: 11 January 2013 / Published: 21 January 2013
Cited by 2 | PDF Full-text (605 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lipid A is a major constituent of the lipopolysaccharides (or endotoxins), which are complex amphiphilic macromolecules anchored in the outer membrane of Gram-negative bacteria. The glycolipid lipid A is known to possess the minimal chemical structure for LPSs endotoxic activity, able to cause
[...] Read more.
Lipid A is a major constituent of the lipopolysaccharides (or endotoxins), which are complex amphiphilic macromolecules anchored in the outer membrane of Gram-negative bacteria. The glycolipid lipid A is known to possess the minimal chemical structure for LPSs endotoxic activity, able to cause septic shock. Lipid A isolated from extremophiles is interesting, since very few cases of pathogenic bacteria have been found among these microorganisms. In some cases their lipid A has shown to have an antagonist activity, i.e., it is able to interact with the immune system of the host without triggering a proinflammatory response by blocking binding of substances that could elicit such a response. However, the relationship between the structure and the activity of these molecules is far from being completely clear. A deeper knowledge of the lipid A chemical structure can help the understanding of these mechanisms. In this manuscript, we present our work on the complete structural characterization of the lipid A obtained from the lipopolysaccharides (LPS) of the haloalkaliphilic bacterium Salinivibrio sharmensis. Lipid A was obtained from the purified LPS by mild acid hydrolysis. The lipid A, which contains different number of fatty acids residues, and its partially deacylated derivatives were completely characterized by means of electrospray ionization Fourier transform ion cyclotron (ESI FT-ICR) mass spectrometry and chemical analysis. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)

Review

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Open AccessReview Structure and Effects of Cyanobacterial Lipopolysaccharides
Mar. Drugs 2015, 13(7), 4217-4230; doi:10.3390/md13074217
Received: 29 May 2015 / Revised: 30 June 2015 / Accepted: 1 July 2015 / Published: 7 July 2015
Cited by 4 | PDF Full-text (1453 KB) | HTML Full-text | XML Full-text
Abstract
Lipopolysaccharide (LPS) is a component of the outer membrane of mainly Gram-negative bacteria and cyanobacteria. The LPS molecules from marine and terrestrial bacteria show structural variations, even among strains within the same species living in the same environment. Cyanobacterial LPS has a unique
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Lipopolysaccharide (LPS) is a component of the outer membrane of mainly Gram-negative bacteria and cyanobacteria. The LPS molecules from marine and terrestrial bacteria show structural variations, even among strains within the same species living in the same environment. Cyanobacterial LPS has a unique structure, since it lacks heptose and 3-deoxy-d-manno-octulosonic acid (also known as keto-deoxyoctulosonate (KDO)), which are present in the core region of common Gram-negative LPS. In addition, the cyanobacterial lipid A region lacks phosphates and contains odd-chain hydroxylated fatty acids. While the role of Gram-negative lipid A in the regulation of the innate immune response through Toll-like Receptor (TLR) 4 signaling is well characterized, the role of the structurally different cyanobacterial lipid A in TLR4 signaling is not well understood. The uncontrolled inflammatory response of TLR4 leads to autoimmune diseases such as sepsis, and thus the less virulent marine cyanobacterial LPS molecules can be effective to inhibit TLR4 signaling. This review highlights the structural comparison of LPS molecules from marine cyanobacteria and Gram-negative bacteria. We discuss the potential use of marine cyanobacterial LPS as a TLR4 antagonist, and the effects of cyanobacterial LPS on humans and marine organisms. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessReview Recognition of LPS by TLR4: Potential for Anti-Inflammatory Therapies
Mar. Drugs 2014, 12(7), 4260-4273; doi:10.3390/md12074260
Received: 8 April 2014 / Revised: 10 June 2014 / Accepted: 4 July 2014 / Published: 23 July 2014
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Abstract
LPS molecules of marine bacteria show structures distinct from terrestrial bacteria, due to the different environment that marine bacteria live in. Because of these different structures, lipid A molecules from marine bacteria are most often poor stimulators of the Toll-like receptor 4 (TLR4)
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LPS molecules of marine bacteria show structures distinct from terrestrial bacteria, due to the different environment that marine bacteria live in. Because of these different structures, lipid A molecules from marine bacteria are most often poor stimulators of the Toll-like receptor 4 (TLR4) pathway. Due to their low stimulatory potential, these lipid A molecules are suggested to be applicable as antagonists of TLR4 signaling in sepsis patients, where this immune response is amplified and unregulated. Antagonizing lipid A molecules might be used for future therapies against sepsis, therapies that currently do not exist. In this review, we will discuss these differences in lipid A structures and their recognition by the immune system. The modifications present in marine lipid A structures are described, and their potential as LPS antagonists will be discussed. Finally, since clinical trials built on antagonizing lipid A molecules have proven unsuccessful, we propose to also focus on different aspects of the TLR4 signaling pathway when searching for new potential drugs. Furthermore, we put forward the notion that bacteria probably already produce inhibitors of TLR4 signaling, making these bacterial products interesting molecules to investigate for future sepsis therapies. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessReview Gram-Negative Marine Bacteria: Structural Features of Lipopolysaccharides and Their Relevance for Economically Important Diseases
Mar. Drugs 2014, 12(5), 2485-2514; doi:10.3390/md12052485
Received: 7 December 2013 / Revised: 3 March 2014 / Accepted: 8 April 2014 / Published: 30 April 2014
Cited by 6 | PDF Full-text (1065 KB) | HTML Full-text | XML Full-text
Abstract
Gram-negative marine bacteria can thrive in harsh oceanic conditions, partly because of the structural diversity of the cell wall and its components, particularly lipopolysaccharide (LPS). LPS is composed of three main parts, an O-antigen, lipid A, and a core region, all of which
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Gram-negative marine bacteria can thrive in harsh oceanic conditions, partly because of the structural diversity of the cell wall and its components, particularly lipopolysaccharide (LPS). LPS is composed of three main parts, an O-antigen, lipid A, and a core region, all of which display immense structural variations among different bacterial species. These components not only provide cell integrity but also elicit an immune response in the host, which ranges from other marine organisms to humans. Toll-like receptor 4 and its homologs are the dedicated receptors that detect LPS and trigger the immune system to respond, often causing a wide variety of inflammatory diseases and even death. This review describes the structural organization of selected LPSes and their association with economically important diseases in marine organisms. In addition, the potential therapeutic use of LPS as an immune adjuvant in different diseases is highlighted. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessReview The Role of Biophysical Parameters in the Antilipopolysaccharide Activities of Antimicrobial Peptides from Marine Fish
Mar. Drugs 2014, 12(3), 1471-1494; doi:10.3390/md12031471
Received: 10 February 2014 / Revised: 3 March 2014 / Accepted: 3 March 2014 / Published: 13 March 2014
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Abstract
Numerous antimicrobial peptides (AMPs) from marine fish have been identified, isolated and characterized. These peptides act as host defense molecules that exert antimicrobial effects by targeting the lipopolysaccharide (LPS) of Gram-negative bacteria. The LPS-AMP interactions are driven by the biophysical properties of AMPs.
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Numerous antimicrobial peptides (AMPs) from marine fish have been identified, isolated and characterized. These peptides act as host defense molecules that exert antimicrobial effects by targeting the lipopolysaccharide (LPS) of Gram-negative bacteria. The LPS-AMP interactions are driven by the biophysical properties of AMPs. In this review, therefore, we will focus on the physiochemical properties of AMPs; that is, the contributions made by their sequences, net charge, hydrophobicity and amphipathicity to their mechanism of action. Moreover, the interactions between LPS and fish AMPs and the structure of fish AMPs with LPS bound will also be discussed. A better understanding of the biophysical properties will be useful in the design of AMPs effective against septic shock and multidrug-resistant bacterial strains, including those that commonly produce wound infections. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
Open AccessReview The Lipopolysaccharide Export Pathway in Escherichia coli: Structure, Organization and Regulated Assembly of the Lpt Machinery
Mar. Drugs 2014, 12(2), 1023-1042; doi:10.3390/md12021023
Received: 15 January 2014 / Revised: 22 January 2014 / Accepted: 28 January 2014 / Published: 17 February 2014
Cited by 12 | PDF Full-text (862 KB) | HTML Full-text | XML Full-text
Abstract
The bacterial outer membrane (OM) is a peculiar biological structure with a unique composition that contributes significantly to the fitness of Gram-negative bacteria in hostile environments. OM components are all synthesized in the cytosol and must, then, be transported efficiently across three compartments
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The bacterial outer membrane (OM) is a peculiar biological structure with a unique composition that contributes significantly to the fitness of Gram-negative bacteria in hostile environments. OM components are all synthesized in the cytosol and must, then, be transported efficiently across three compartments to the cell surface. Lipopolysaccharide (LPS) is a unique glycolipid that paves the outer leaflet of the OM. Transport of this complex molecule poses several problems to the cells due to its amphipatic nature. In this review, the multiprotein machinery devoted to LPS transport to the OM is discussed together with the challenges associated with this process and the solutions that cells have evolved to address the problem of LPS biogenesis. Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)

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Open AccessCorrection Correction: Structural Studies of the Lipopolysaccharide from the Fish Pathogen Aeromonas veronii Strain Bs19, Serotype O16. Mar. Drugs 2014, 12, 1298–1316
Mar. Drugs 2014, 12(9), 4741-4742; doi:10.3390/md12094741
Received: 25 June 2014 / Revised: 30 June 2014 / Accepted: 4 July 2014 / Published: 5 September 2014
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Abstract We found one editorial mistake in our published paper [1]. In Line 2 of Table 4, the same composition of sugars is given for the C4 and C5 species (in the C5 species, one residue: 6dHexNAc has been missed). [...] Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)

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