LIPOPOLYSACCHARIDE

'Lipopolysaccharide' ('LPS') is a large molecule consisting of a lipid and a polysaccharide (carbohydrate) joined by a covalent bond.

Contents

Functions

Composition

Lipid A

Core oligosaccharide

O-antigen

LPS modifications

Variability and effect upon specificity

Functions

Diversity

References

See also

External links

Functions

LPS is a major component of the outer membrane of Gram-negative bacteria, contributing greatly to the structural integrity of the bacteria, and protecting the membrane from certain kinds of chemical attack. LPS is an endotoxin, and induces a strong response from normal animal immune systems. The only Gram-positive bacteria that possesses LPS is ''Listeria monocytogenes'', the common infective agent in unpasteurized milk.
LPS acts as the prototypical endotoxin, because it binds the CD14/TLR4/MD2 receptor complex, which promotes the secretion of pro-inflammatory cytokines in many cell types, but especially in macrophages. An "LPS challenge" in immunology is the exposing of the subject to an LPS which may act as a toxin.

LPS also increases the negative charge of the cell membrane and helps stabilize the overall membrane structure.

Composition

It comprises three parts:

★ polysaccharide (O) side chains

★ core oligosaccharide

★ lipid A

Lipid A

Lipid A contains unusual fatty acids (''e.g.'' hydroxy-myristic acid) and is embedded into the outer membrane while the rest of the LPS projects form the surface.

Core oligosaccharide

Core oligosaccharide contains unusual sugars (''e.g.'' KDO, keto-deoxyoctulonate and heptose).
The core oligosaccharide is attached to lipid A, which is also in part responsible for the toxicity of gram-negative bacteria.

O-antigen

The polysaccharide side chain is referred to as the O-antigen of the bacteria.
O side chain (O-antigen) is also a polysaccharide chain that extends from the core polysaccharide. The composition of the O side chain varies between different gram-negative bacterial strains. O side chains are easily recognized by the antibodies of the host, however, the nature of the chain can easily be modified by Gram-negative bacteria to avoid detection. The structure of the core and the O-antigen is often determined by methylation analysis or NMR-spectroscopy.

LPS modifications

The making of LPS can be modified in order to present a specific sugar structure. Those can be recognised by either other LPS (which enables to inhibit LPS toxins) or glycosyltransferases which use those sugar structure to add more specific sugars.

Variability and effect upon specificity

O-antigens (the outer carbohydrates) are the most variable portion of the LPS molecule, imparting the antigenic specificity. In contrast, lipid A is the most conserved part. However, —lipid A composition also may vary (eg in number and nature of acyl chains even within or between genera). Some of these variations may impart antagonistic properties to these LPS. For example Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) is a potent antagonist of LPS in human cells, but is an agonist in hamster and equine cells.
It has been speculated that conical Lipid A (eg from E coli) are more agonistic, less conical lipid A like those of Porphyromonas gingivalis may activate a different signal (TLR2 instead of TLR4), and completely cylindrical lipid A like that of Rhodobacter sphaeroides is antagonistic to TLRs.^[1][2]

Functions

LPS function has been under experimental research for several years due to its role in activating many transcription factors.
LPS also produces many types of mediators involved in septic shock.

Diversity

Lipololysaccharide gene clusters are highly variable between different strains, subspecies, species of bacterial pathogens of plants and animals.^[3][4]

References

1. Does the shape of lipid A determine the interaction of LPS with Toll-like receptors?, Netea M et al, , , Trends Immunol, 2002
2. Intrinsic conformation of lipid A is responsible for agonistic and antagonistic activity, Seydel U, Oikawa M, Fukase K, Kusumoto S, Brandenburg K, , , Eur J Biochem, 2000
3. Genomic organization of LPS-specific loci, Reeves P, Wang L, , , Curr Top Microbiol Immunol, 2002
4. Variation suggestive of horizontal gene transfer at a lipopolysaccharide (lps) biosynthetic locus in Xanthomonas oryzae pv. oryzae, the bacterial leaf blight pathogen of rice, Patil P, Sonti R, , , BMC Microbiol, 2004

See also

★ Endotoxin

★ Mucopolysaccharide

External links

★