scholarly journals The Unusual Lipid A Structure and Immunoinhibitory Activity of LPS from Marine Bacteria Echinicola pacifica KMM 6172T and Echinicola vietnamensis KMM 6221T

2021 ◽  
Vol 9 (12) ◽  
pp. 2552
Author(s):  
Molly Dorothy Pither ◽  
Giuseppe Mantova ◽  
Elena Scaglione ◽  
Chiara Pagliuca ◽  
Roberta Colicchio ◽  
...  
Keyword(s):  
Marine Bacteria ◽  
Lipid A ◽  
Fatty Acid Content ◽  
Membrane System ◽  
Marine Microorganisms ◽  
Gram Negative ◽  
Structural Modifications ◽  
Chemical Structures ◽  
Marine Habitats ◽  
Lipid A Structure

Gram-negative bacteria experiencing marine habitats are constantly exposed to stressful conditions dictating their survival and proliferation. In response to these selective pressures, marine microorganisms adapt their membrane system to ensure protection and dynamicity in order to face the highly mutable sea environments. As an integral part of the Gram-negative outer membrane, structural modifications are commonly observed in the lipopolysaccharide (LPS) molecule; these mainly involve its glycolipid portion, i.e., the lipid A, mostly with regard to fatty acid content, to counterbalance the alterations caused by chemical and physical agents. As a consequence, unusual structural chemical features are frequently encountered in the lipid A of marine bacteria. By a combination of data attained from chemical, MALDI-TOF mass spectrometry (MS), and MS/MS analyses, here, we describe the structural characterization of the lipid A isolated from two marine bacteria of the Echinicola genus, i.e., E. pacifica KMM 6172T and E. vietnamensis KMM 6221T. This study showed for both strains a complex blend of mono-phosphorylated tri- and tetra-acylated lipid A species carrying an additional sugar moiety, a d-galacturonic acid, on the glucosamine backbone. The unusual chemical structures are reflected in a molecule that only scantly activates the immune response upon its binding to the LPS innate immunity receptor, the TLR4-MD-2 complex. Strikingly, both LPS potently inhibited the toxic effects of proinflammatory Salmonella LPS on human TLR4/MD-2.

scholarly journals The Structure of the Lipid A of Gram-Negative Cold-Adapted Bacteria Isolated from Antarctic Environments

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 592
Author(s):  
Flaviana Di Lorenzo ◽  
Francesca Crisafi ◽  
Violetta La Cono ◽  
Michail M. Yakimov ◽  
Antonio Molinaro ◽  
...  
Keyword(s):  
Lipid A ◽  
Compositional Analysis ◽  
Survival Strategies ◽  
Gram Negative ◽  
Cold Adapted ◽  
Structural Modifications ◽  
Terra Nova Bay ◽  
Drug Synthesis ◽  
Acyl Chains ◽  
Main Component

Gram-negative Antarctic bacteria adopt survival strategies to live and proliferate in an extremely cold environment. Unusual chemical modifications of the lipopolysaccharide (LPS) and the main component of their outer membrane are among the tricks adopted to allow the maintenance of an optimum membrane fluidity even at particularly low temperatures. In particular, the LPS’ glycolipid moiety, the lipid A, typically undergoes several structural modifications comprising desaturation of the acyl chains, reduction in their length and increase in their branching. The investigation of the structure of the lipid A from cold-adapted bacteria is, therefore, crucial to understand the mechanisms underlying the cold adaptation phenomenon. Here we describe the structural elucidation of the highly heterogenous lipid A from three psychrophiles isolated from Terra Nova Bay, Antarctica. All the lipid A structures have been determined by merging data that was attained from the compositional analysis with information from a matrix-assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry (MS) and MS2 investigation. As lipid A is also involved in a structure-dependent elicitation of innate immune response in mammals, the structural characterization of lipid A from such extremophile bacteria is also of great interest from the perspective of drug synthesis and development inspired by natural sources.

scholarly journals Variation, Modification and Engineering of Lipid A in Endotoxin of Gram-Negative Bacteria

2021 ◽  
Vol 22 (5) ◽  
pp. 2281
Author(s):  
Kazuyoshi Kawahara
Keyword(s):  
Fatty Acids ◽  
Lipid A ◽  
Hydroxy Fatty Acids ◽  
Hydroxyl Groups ◽  
Gram Negative Bacteria ◽  
Vaccine Adjuvants ◽  
Phagocytic Cells ◽  
Gram Negative ◽  
Electrostatic Charges ◽  
Lipid A Structure

Lipid A of Gram-negative bacteria is known to represent a central role for the immunological activity of endotoxin. Chemical structure and biosynthetic pathways as well as specific receptors on phagocytic cells had been clarified by the beginning of the 21st century. Although the lipid A of enterobacteria including Escherichia coli share a common structure, other Gram-negative bacteria belonging to various classes of the phylum Proteobacteria and other taxonomical groups show wide variety of lipid A structure with relatively decreased endotoxic activity compared to that of E. coli. The structural diversity is produced from the difference of chain length of 3-hydroxy fatty acids and non-hydroxy fatty acids linked to their hydroxyl groups. In some bacteria, glucosamine in the backbone is substituted by another amino sugar, or phosphate groups bound to the backbone are modified. The variation of structure is also introduced by the enzymes that can modify electrostatic charges or acylation profiles of lipid A during or after its synthesis. Furthermore, lipid A structure can be artificially modified or engineered by the disruption and introduction of biosynthetic genes especially those of acyltransferases. These technologies may produce novel vaccine adjuvants or antagonistic drugs derived from endotoxin in the future.

Biosynthesis, transport, and modification of lipid A

2004 ◽  
Vol 82 (1) ◽  
pp. 71-86 ◽  
Author(s):  
M Stephen Trent
Keyword(s):  
Molecular Mechanisms ◽  
Lipid A ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Chemical Structures ◽  
Bioactive Component ◽  
Genes Encoding ◽  
Major Surface ◽  
Surface Remodeling ◽  
Enzymatic Machinery

Lipopolysaccharide (LPS) is the major surface molecule of Gram-negative bacteria and consists of three distinct structural domains: O-antigen, core, and lipid A. The lipid A (endotoxin) domain of LPS is a unique, glucosamine-based phospholipid that serves as the hydrophobic anchor of LPS and is the bioactive component of the molecule that is associated with Gram-negative septic shock. The structural genes encoding the enzymes required for the biosynthesis of Escherchia coli lipid A have been identified and characterized. Lipid A is often viewed as a constitutively synthesized structural molecule. However, determination of the exact chemical structures of lipid A from diverse Gram-negative bacteria shows that the molecule can be further modified in response to environmental stimuli. These modifications have been implicated in virulence of pathogenic Gram-negative bacteria and represent one of the molecular mechanisms of microbial surface remodeling used by bacteria to help evade the innate immune response. The intent of this review is to discuss the enzymatic machinery involved in the biosynthesis of lipid A, transport of the molecule, and finally, those enzymes involved in the modification of its structure in response to environmental stimuli.Key words: lipopolysaccharides, lipid A, endotoxin, outer membrane, MsbA.

A Freeze-Etch Study of Acinetobacter SP. Grown on a Hydrocarbon Substrate

1974 ◽  
Vol 32 ◽  
pp. 174-175
Author(s):  
C. L. Scott ◽  
W. R. Finnerty
Keyword(s):  
Membrane System ◽  
Structural Distortion ◽  
Intracytoplasmic Membrane ◽  
Gram Negative ◽  
Sectioned Material ◽  
Acinetobacter Sp

Acinetobacter sp. HO-1-N, a gram-negative hydrocarbon oxidizing bacterium previously designated Micrococcus cerificans, has been shown to sequester the hydrocarbon into intracytoplasmic pools as a result of growth on this substrate. In hydrocarbon grown cells, an intracytoplasmic membrane system was also observed along with a doubling of cellular phospholipids (Z). However, using conventional dehydration and embedding procedures in preparing thin sectioned material, the hydrocarbon is extracted from the cells. This may lead to structural distortion, consequently, the freeze-etch technique was applied to preserve the integrity of the cell.

scholarly journals Formation of Amphiphilic Molecules from the Most Common Marine Polysaccharides, toward a Sustainable Alternative?

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4445
Author(s):  
Tiphaine Wong ◽  
Lorette Brault ◽  
Eric Gasparotto ◽  
Romuald Vallée ◽  
Pierre-Yves Morvan ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Carboxylic Acid ◽  
Bioactive Compounds ◽  
Biological Properties ◽  
Cross Linking ◽  
Structural Modifications ◽  
Chemical Structures ◽  
Amphiphilic Molecules

Marine polysaccharides are part of the huge seaweeds resources and present many applications for several industries. In order to widen their potential as additives or bioactive compounds, some structural modifications have been studied. Among them, simple hydrophobization reactions have been developed in order to yield to grafted polysaccharides bearing acyl-, aryl-, alkyl-, and alkenyl-groups or fatty acid chains. The resulting polymers are able to present modified physicochemical and/or biological properties of interest in the current pharmaceutical, cosmetics, or food fields. This review covers the chemical structures of the main marine polysaccharides, and then focuses on their structural modifications, and especially on hydrophobization reactions mainly esterification, acylation, alkylation, amidation, or even cross-linking reaction on native hydroxyl-, amine, or carboxylic acid functions. Finally, the question of the necessary requirement for more sustainable processes around these structural modulations of marine polysaccharides is addressed, considering the development of greener technologies applied to traditional polysaccharides.

scholarly journals Analyses of Lipid A Diversity in Gram-Negative Intestinal Bacteria Using Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 197
Author(s):  
Nobuyuki Okahashi ◽  
Masahiro Ueda ◽  
Fumio Matsuda ◽  
Makoto Arita
Keyword(s):  
Mass Spectrometry ◽  
Immune Response ◽  
Liquid Chromatography ◽  
Mammalian Cells ◽  
Lipid A ◽  
Acyl Chain ◽  
Time Of Flight ◽  
Intestinal Bacteria ◽  
Gram Negative ◽  
Flight Mass Spectrometry

Lipid A is a characteristic molecule of Gram-negative bacteria that elicits an immune response in mammalian cells. The presence of structurally diverse lipid A types in the human gut bacteria has been suggested before, and this appears associated with the immune response. However, lipid A structures and their quantitative heterogeneity have not been well characterized. In this study, a method of analysis for lipid A using liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) was developed and applied to the analyses of Escherichia coli and Bacteroidetes strains. In general, phosphate compounds adsorb on stainless-steel piping and cause peak tailing, but the use of an ammonia-containing alkaline solvent produced sharp lipid A peaks with high sensitivity. The method was applied to E. coli strains, and revealed the accumulation of lipid A with abnormal acyl side chains in knockout strains as well as known diphosphoryl hexa-acylated lipid A in a wild-type strain. The analysis of nine representative strains of Bacteroidetes showed the presence of monophosphoryl penta-acylated lipid A characterized by a highly heterogeneous main acyl chain length. Comparison of the structures and amounts of lipid A among the strains suggested a relationship between lipid A profiles and the phylogenetic classification of the strains.

scholarly journals On-surface activation of benzylic C-H bonds for the synthesis of pentagon-fused graphene nanoribbons

Nano Research ◽  
2021 ◽  
Author(s):  
Xiushang Xu ◽  
Marco Di Giovannantonio ◽  
José I. Urgel ◽  
Carlo A. Pignedoli ◽  
Pascal Ruffieux ◽  
...  
Keyword(s):  
Carbon Nanomaterials ◽  
Graphene Nanoribbons ◽  
Gold Surface ◽  
Fine Tuning ◽  
Uniform Structure ◽  
Methyl Groups ◽  
Structural Modifications ◽  
Force Microscopy ◽  
Chemical Structures ◽  
Atomic Force

AbstractGraphene nanoribbons (GNRs) have potential for applications in electronic devices. A key issue, thereby, is the fine-tuning of their electronic characteristics, which can be achieved through subtle structural modifications. These are not limited to the conventional armchair, zigzag, and cove edges, but also possible through incorporation of non-hexagonal rings. On-surface synthesis enables the fabrication and visualization of GNRs with atomically precise chemical structures, but strategies for the incorporation of non-hexagonal rings have been underexplored. Herein, we describe the on-surface synthesis of armchair-edged GNRs with incorporated five-membered rings through the C-H activation and cyclization of benzylic methyl groups. Ortho-Tolyl-substituted dibromobianthryl was employed as the precursor monomer, and visualization of the resulting structures after annealing at 300 °C on a gold surface by high-resolution noncontact atomic force microscopy clearly revealed the formation of methylene-bridged pentagons at the GNR edges. These persisted after annealing at 340 °C, along with a few fully conjugated pentagons having singly-hydrogenated apexes. The benzylic methyl groups could also migrate or cleave-off, resulting in defects lacking the five-membered rings. Moreover, unexpected and unique structural rearrangements, including the formation of embedded heptagons, were observed. Despite the coexistence of different reaction pathways that hamper selective synthesis of a uniform structure, our results provide novel insights into on-surface reactions en route to functional, non-benzenoid carbon nanomaterials.

scholarly journals Design, Synthesis and Biological Evaluation of Novel Benzothiazole Based [1,2,4]Triazolo[4,3-c]quinazoline Derivatives

2020 ◽  
Vol 32 (3) ◽  
pp. 580-586
Author(s):  
Ranjit V. Gadhave ◽  
Bhanudas S. Kuchekar
Keyword(s):  
Biological Evaluation ◽  
Bacterial Strains ◽  
Active Compounds ◽  
Design Synthesis ◽  
Structural Modifications ◽  
E Coli ◽  
Chemical Structures ◽  
Ft Ir ◽  
Antioxidant Agent

A new series of N-(benzo[d]thiazol-2-yl)-[1,2,4]triazolo[4,3-c]quinazoline-5-carboxamide derivatives were synthesized by condensation of [1,2,4]triazolo[4,3-c]quinazoline-5-carboxylate derivatives with substituted benzothiazoles. The chemical structures of the synthesized compounds were confirmed by FT-IR, MS and 1H NMR spectra. Designed triazoloquinazoline derivatives were docked with oxido-reductase enzyme (PDB Code 4h1j) and DNA gyrase enzyme (PDB Code 3g75). Based on high binding affinity score, the best compound were selected for synthesis and subjected to in vitro antioxidant and antibacterial activity. Compounds 7a and 7d were found to be most active compounds as antioxidant agent among this series when compared with ascorbic acid. Compounds 7a, 7d and 7f were found to be most active compounds as an antibacterial agents among this series when compared with ciprofloxacin against bacterial strains such as S. aureus (ATCC 25923), E. coli (ATCC 25922) and P. aeruginosa (ATCC 27853). Study revealed that the most active compounds after structural modifications can be exploited as lead molecules for other pharmacological activities such as anti-inflammatory, anticancer and antidepressant activities.

An enumeration of natural products from microbial, marine and terrestrial sources

2020 ◽  
Vol 5 (8) ◽  
Author(s):  
Fidele Ntie-Kang ◽  
Daniel Svozil
Keyword(s):  
Amino Acids ◽  
Natural Products ◽  
Biologically Active ◽  
Lead Compound ◽  
Chemical Databases ◽  
Natural Sources ◽  
Chemical Structures ◽  
Chemically Modified ◽  
Marine Habitats ◽  
Metabolic Properties

AbstractThe discovery of a new drug is a multidisciplinary and very costly task. One of the major steps is the identification of a lead compound, i.e. a compound with a certain degree of potency and that can be chemically modified to improve its activity, metabolic properties, and pharmacokinetics profiles. Terrestrial sources (plants and fungi), microbes and marine organisms are abundant resources for the discovery of new structurally diverse and biologically active compounds. In this chapter, an attempt has been made to quantify the numbers of known published chemical structures (available in chemical databases) from natural sources. Emphasis has been laid on the number of unique compounds, the most abundant compound classes and the distribution of compounds in terrestrial and marine habitats. It was observed, from the recent investigations, that ~500,000 known natural products (NPs) exist in the literature. About 70 % of all NPs come from plants, terpenoids being the most represented compound class (except in bacteria, where amino acids, peptides, and polyketides are the most abundant compound classes). About 2,000 NPs have been co-crystallized in PDB structures.

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