structure of lps

7/30/2019 Structure of LPS

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Structure

Intact bacterial lipopolysaccharides are macromolecules of molecular mass 10-20 kDa made up of three structuralcomponents (see Figure 1):

A hydrophobic lipid section, lipid A, which is responsible for the toxic properties of the molecule,

A hydrophilic core polysaccharide chain, and

A repeating hydrophilic O-antigenic oligosaccharide side chain that is specific to the bacterial serotype.1

The lipid A core is made up of a -glucosamine-(16)-glucosamine-1-phosphate base with fatty acid esters attachedto both carbohydrates. The acyl chain length and number of acyl groups may vary between bacterial species but arerelatively conserved within a species. The inner polysaccharide core typically contains between 1 and 4 molecules ofthe KDO (3-deoxy--D-manno-octulosonic acid) attached to the disaccharide core. KDO is specifically associated withlipopolysaccharide, and biologically active lipid A was thought to require at least one KDO residue for bacterialsurvival.2However, an Escherichia coliK-12 suppressor strain that is KDO deficient demonstrates that the KDOrequirement is not absolute for viability.3

The KDO-containing inner core also is modified with heptulose (ketoheptose) monosaccharides, the most common ofwhich is L-glycero--D-manno-heptopyranose. The inner core glycan residues are typically phosphorylated or modifiedwith phosphate-containing groups, e.g., pyrophosphate or 2-aminoethylphosphate. The phosphate groups of

lipopolysaccharides increase the overall negative charge of the cell membrane and help to stabilize the structure.

The outer core of the lipopolysaccharide contains more common hexoses, including glucose, galactose, and N-acetylglucosamine and is structurally more diverse than the inner core.

The O-antigen is a repeating oligosaccharide unit typically comprised of two to six sugars. The O-antigen is theprimary structural constituent of lipopolysaccharide that differentiates bacteria. The distinctive O-antigen structureshave been used to identify and assign serogroups to Escherichia coli, Salmonella enterica, and Vibrio

Figure 1. General structurefor bacteriallipopolysaccharides. Seethe text for detailedexplanation regarding eachsection.Abbreviations: KDO:3-deoxy--D-mannooctulosonicacid; Hep: Heptulose

(ketoheptose); NGa:Galactosamine; NGc:Glucosamine.
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cholerae.4Lipopolysaccharides from rough mutant strains of E. colilack the O-antigen portion of the structure.

The core section and the lipid A section of a lipopolysaccharide may have some variability in structure, while the O-antigen has a high degree of structural variability as well as variability in the number of repeating units. Thesedifferences result in a significant amount of heterogeneity in LPS preparations. Since LPS is heterogeneous and tendsto form aggregates of varying sizes, there is a reported "molecular mass" range for these aggregates of 1-4 millionDalton or greater. When the LPS is treated with sodium dodecyl sulfate (SDS) and heat, the molecular mass is~50-100 kDa.5

Functions and Applications

Within Gram-negative bacteria, the membrane lipopolysaccharides protect the bacterium against the action of bilesalts and lipophilic antibiotics.6

Lipopolysaccharides are heat stable endotoxins and have long been recognized as a key factor in septic shock(septicemia) in humans1,7and, more generally, in inducing a strong immune response in normal mammalian cells. Thelipid A moiety has been identified as critical to the endotoxin activity of lipopolysaccharide. This was demonstrated,Galanos, et al., by finding identical bioactive results, including endotoxic activity, between synthetic and natural-sourced E. colilipid A preparations.8The active receptor for lipopolysaccharide has been identified as theCD14/TLR4/MD2 receptor complex, which promotes the secretion of proinflammatory cytokines including tumornecrosis factor- and interleukin-1.9While the lipid A component is primarily responsible for immune responseactivation, the polysaccharide component of Salmonella enterica LPS is also necessary for NF-B activation.10

Lipopolysaccharide preparations have been used in research for the elucidation of LPSstructure,11metabolism,12immunology,13physiology,14toxicity,15and biosynthesis.16They have also been used to induce

synthesis and secretion of growth promoting factors such as interleukins.17,18

Because of its connection to septicemia,lipopolysaccharide has been studied to identify possible targets for antibodies and inhibitors to LPS biosynthesis.19,20

Extraction and Purification

Lipopolysaccharides can be prepared by extraction from TCA,21phenol,22,23or phenol-chloroform-petroleum ether (forrough strains).24TCA extracted lipopolysaccharides are structurally similar to the phenol extracted ones, with similarelectrophoretic patterns and endotoxicity. The primary differences are in the amounts of nucleic acid and proteincontaminants remaining after extraction. The TCA extracts contain ~2% RNA and ~10% denatured proteins, whilephenol extracts contain up to 60% RNA and


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Some researchers doubt reports of generalized toxic effects attributed to all lipopolysaccharides, in particular,

forcyanobacteria.[1]

Composition [edit]

It comprises three parts:

1. O antigen(orO polysaccharide)

2. Core oligosaccharide

3. Lipid AO-antigen [edit]

A repetitiveglycanpolymercontained within an LPS is referred to as the Oantigen, Opolysaccharide, or O side-chain of the

bacteria. The O antigen is attached to the core oligosaccharide, and comprises the outermost domain of the LPS molecule.

The composition of the O chain varies from strain to strain. For example, there are over 160 different O antigen structures

produced by differentE. colistrains.[2]

The presence or absence of O chains determines whether the LPS is considered rough

or smooth. Full-length O-chains would render the LPS smooth, whereas the absence or reduction of O-chains would make the

LPS rough.[3]

Bacteria with rough LPS usually have more penetrable cell membranes to hydrophobic antibiotics, since a rough

LPS is morehydrophobic.[4]

O antigen is exposed on the very outer surface of the bacterial cell, and, as a consequence, is a

target for recognition by hostantibodies.
http://en.wikipedia.org/wiki/Cyanobacteriahttp://en.wikipedia.org/wiki/Cyanobacteriahttp://en.wikipedia.org/wiki/O_antigen#cite_note-1http://en.wikipedia.org/wiki/O_antigen#cite_note-1http://en.wikipedia.org/wiki/O_antigen#cite_note-1http://en.wikipedia.org/w/index.php?title=Lipopolysaccharide&action=edit&section=2http://en.wikipedia.org/w/index.php?title=Lipopolysaccharide&action=edit&section=2http://en.wikipedia.org/w/index.php?title=Lipopolysaccharide&action=edit&section=2http://en.wikipedia.org/wiki/O_antigenhttp://en.wikipedia.org/wiki/O_antigenhttp://en.wikipedia.org/wiki/O_antigenhttp://en.wikipedia.org/wiki/O_antigenhttp://en.wikipedia.org/wiki/O_antigenhttp://en.wikipedia.org/wiki/Core_oligosaccharidehttp://en.wikipedia.org/wiki/Core_oligosaccharidehttp://en.wikipedia.org/wiki/Lipid_Ahttp://en.wikipedia.org/wiki/Lipid_Ahttp://en.wikipedia.org/w/index.php?title=Lipopolysaccharide&action=edit&section=3http://en.wikipedia.org/w/index.php?title=Lipopolysaccharide&action=edit&section=3http://en.wikipedia.org/w/index.php?title=Lipopolysaccharide&action=edit&section=3http://en.wikipedia.org/wiki/Glycanhttp://en.wikipedia.org/wiki/Glycanhttp://en.wikipedia.org/wiki/Polymerhttp://en.wikipedia.org/wiki/Polymerhttp://en.wikipedia.org/wiki/Polymerhttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Polysaccharidehttp://en.wikipedia.org/wiki/Polysaccharidehttp://en.wikipedia.org/wiki/Polysaccharidehttp://en.wikipedia.org/wiki/E._colihttp://en.wikipedia.org/wiki/E._colihttp://en.wikipedia.org/wiki/E._colihttp://en.wikipedia.org/wiki/O_antigen#cite_note-2http://en.wikipedia.org/wiki/O_antigen#cite_note-2http://en.wikipedia.org/wiki/O_antigen#cite_note-2http://en.wikipedia.org/wiki/O_antigen#cite_note-3http://en.wikipedia.org/wiki/O_antigen#cite_note-3http://en.wikipedia.org/wiki/O_antigen#cite_note-3http://en.wikipedia.org/wiki/Hydrophobichttp://en.wikipedia.org/wiki/Hydrophobichttp://en.wikipedia.org/wiki/O_antigen#cite_note-4http://en.wikipedia.org/wiki/O_antigen#cite_note-4http://en.wikipedia.org/wiki/O_antigen#cite_note-4http://en.wikipedia.org/wiki/Antibodyhttp://en.wikipedia.org/wiki/Antibodyhttp://en.wikipedia.org/wiki/Antibodyhttp://en.wikipedia.org/wiki/Antibodyhttp://en.wikipedia.org/wiki/O_antigen#cite_note-4http://en.wikipedia.org/wiki/Hydrophobichttp://en.wikipedia.org/wiki/O_antigen#cite_note-3http://en.wikipedia.org/wiki/O_antigen#cite_note-2http://en.wikipedia.org/wiki/E._colihttp://en.wikipedia.org/wiki/Polysaccharidehttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Polymerhttp://en.wikipedia.org/wiki/Glycanhttp://en.wikipedia.org/w/index.php?title=Lipopolysaccharide&action=edit&section=3http://en.wikipedia.org/wiki/Lipid_Ahttp://en.wikipedia.org/wiki/Core_oligosaccharidehttp://en.wikipedia.org/wiki/O_antigenhttp://en.wikipedia.org/wiki/O_antigenhttp://en.wikipedia.org/w/index.php?title=Lipopolysaccharide&action=edit&section=2http://en.wikipedia.org/wiki/O_antigen#cite_note-1http://en.wikipedia.org/wiki/Cyanobacteria

structure of lps

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