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Lipopolysaccharide
 
 
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Lipopolysaccharides (LPS) , also known as lipoglycans, are large molecule
Molecule

In chemistry, a molecule is defined as a sufficiently stable, electric charge neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds....
s consisting of a lipid
Lipid

Lipids are broadly defined as any fat-soluble , naturally-occurring molecule, such as fats, oils, waxes, cholesterol, sterols, fat-soluble vitamins , monoglycerides, diglycerides, phospholipids, and others....
 and a polysaccharide
Polysaccharide

Polysaccharides are relatively complex carbohydrates. They are polymers made up of many monosaccharides joined together by glycosidic bonds. They are therefore very large, often branched, macromolecules....
 joined by a covalent bond
Covalent bond

A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms, or between atoms and other covalent bonds....
; they are found in the outer membrane
Outer membrane

The bacterial outer membrane is found in Gram-negative bacteria. Its composition is distinct from that of the cytoplasmic membrane - among other things, the outer leaflet of the membrane include a complex lipopolysaccharide whose lipid portion acts as an endotoxin - and it is linked to the cell's peptidoglycan by Braun's lipoprotein....
 of Gram-negative
Gram-negative

Gram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color....
 bacteria, act as endotoxin
Endotoxin

Endotoxins are toxins associated with certain bacteria. Classically, an "endotoxin" is a toxin which, unlike an "exotoxin", is not secreted in soluble form by live bacteria, but is a structural component in the bacteria which is released mainly when bacteria are lysis....
s and elicit strong immune responses in animals.

is a major component of the outer membrane
Outer membrane

The bacterial outer membrane is found in Gram-negative bacteria. Its composition is distinct from that of the cytoplasmic membrane - among other things, the outer leaflet of the membrane include a complex lipopolysaccharide whose lipid portion acts as an endotoxin - and it is linked to the cell's peptidoglycan by Braun's lipoprotein....
 of Gram-negative
Gram-negative

Gram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color....
 bacteria, contributing greatly to the structural integrity of the bacteria, and protecting the membrane from certain kinds of chemical attack.






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Lipopolysaccharides (LPS) , also known as lipoglycans, are large molecule
Molecule

In chemistry, a molecule is defined as a sufficiently stable, electric charge neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds....
s consisting of a lipid
Lipid

Lipids are broadly defined as any fat-soluble , naturally-occurring molecule, such as fats, oils, waxes, cholesterol, sterols, fat-soluble vitamins , monoglycerides, diglycerides, phospholipids, and others....
 and a polysaccharide
Polysaccharide

Polysaccharides are relatively complex carbohydrates. They are polymers made up of many monosaccharides joined together by glycosidic bonds. They are therefore very large, often branched, macromolecules....
 joined by a covalent bond
Covalent bond

A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms, or between atoms and other covalent bonds....
; they are found in the outer membrane
Outer membrane

The bacterial outer membrane is found in Gram-negative bacteria. Its composition is distinct from that of the cytoplasmic membrane - among other things, the outer leaflet of the membrane include a complex lipopolysaccharide whose lipid portion acts as an endotoxin - and it is linked to the cell's peptidoglycan by Braun's lipoprotein....
 of Gram-negative
Gram-negative

Gram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color....
 bacteria, act as endotoxin
Endotoxin

Endotoxins are toxins associated with certain bacteria. Classically, an "endotoxin" is a toxin which, unlike an "exotoxin", is not secreted in soluble form by live bacteria, but is a structural component in the bacteria which is released mainly when bacteria are lysis....
s and elicit strong immune responses in animals.

Functions

LPS is a major component of the outer membrane
Outer membrane

The bacterial outer membrane is found in Gram-negative bacteria. Its composition is distinct from that of the cytoplasmic membrane - among other things, the outer leaflet of the membrane include a complex lipopolysaccharide whose lipid portion acts as an endotoxin - and it is linked to the cell's peptidoglycan by Braun's lipoprotein....
 of Gram-negative
Gram-negative

Gram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color....
 bacteria, contributing greatly to the structural integrity of the bacteria, and protecting the membrane from certain kinds of chemical attack. LPS also increases the negative charge of the cell membrane
Cell membrane

The cell membrane is the interface between the cellular machinery inside the cell and the fluid outside.It is a semipermeable lipid bilayer found in all cell ....
 and helps stabilize the overall membrane structure. It is of crucial importance to gram negative bacterial cells; death results if it is mutated or removed. LPS is an endotoxin
Endotoxin

Endotoxins are toxins associated with certain bacteria. Classically, an "endotoxin" is a toxin which, unlike an "exotoxin", is not secreted in soluble form by live bacteria, but is a structural component in the bacteria which is released mainly when bacteria are lysis....
, and induces a strong response from normal animal immune system
Immune system

An immune system is a collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells....
s. It acts as the prototypical endotoxin because it binds the CD14
Cluster of differentiation

The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on leukocytes. CD molecules can act in numerous ways, often acting as receptor or ligand important to the cell....
/TLR4
TLR 4

Toll-like receptor 4, also known as TLR4, is a human gene. TLR 4 is a toll-like receptor. It detects lipopolysaccharide on Gram-negative bacteria and is thus important in the activation of the innate immune system....
/MD2
Lymphocyte antigen 96

Lymphocyte antigen 96, also known as LY96, is a human gene.The protein encoded by this gene is involved in binding lipopolysaccharide with TLR 4....
 receptor
Receptor (biochemistry)

In biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach....
 complex, which promotes the secretion of pro-inflammatory cytokine
Cytokine

Cytokines are a category of signaling molecules that, like hormones and neurotransmitters, are used extensively in cell communication. They are proteins, peptides or glycoproteins....
s 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 is additionally an exogenous pyrogen (external fever-inducing compound).

With the Lipopolysaccharide being of crucial importance to gram negative bacterial cells, it is therefore a prime target for future antimicrobial
Antimicrobial

An antimicrobial is a substance that kills or inhibits the growth of microbes such as bacteria, fungi, protozoals or viruses. Antimicrobial drugs either kill microbes or prevent the growth of microbes ....
 substances.

Some researchers believe that generalized toxic effects attributed to all lipolysaccharides, and particularly cyanobacterial ones, are not always supported by rigorous research.

Composition


It comprises three parts:
  1. Polysaccharide
    Polysaccharide

    Polysaccharides are relatively complex carbohydrates. They are polymers made up of many monosaccharides joined together by glycosidic bonds. They are therefore very large, often branched, macromolecules....
     (O) side chain
    Side chain

    A side chain in organic chemistry and biochemistry is a part of a molecule that is attached to a core structure. The placeholder R is often used as a generic placeholder for side chains, the R historically being derived from radical or rest....
    s
  2. Core polysaccharide (core oligosaccharide in genus Neisseria
    Neisseria

    Neisseria is a genus of Gram bacterium included among the proteobacteria, a large group of Gram-negative forms. Neisseria are Diplococcus that resemble coffee beans when viewed microscopically....
    )
  3. Lipid A
    Lipid A

    Lipid A is a lipid component of an endotoxin held responsible for toxicity of Gram-negative bacteria. It is the innermost of the three regions of the lipopolysaccharide molecule, and its hydrophobe nature allows it to anchor the LPS to the outer membrane....


Lipid A

Lipid A contains unusual fatty acid
Fatty acid

In chemistry, especially biochemistry, a fatty acid is a carboxylic acid often with a long unbranched aliphatic tail , which is either saturation or Unsaturated compound....
s ('e.g.' hydroxy-myristic acid
Myristic acid

Myristic acid, also called tetradecanoic acid or 14:0 is a common saturated fatty acid with the molecular formula CH312COOH....
) and is embedded into the outer membrane while the rest of the LPS projects from the surface. Lipid A is a disaccharide with multiple fatty acid tails reaching into the membrane. This is the key in the toxicity. When bacterial cells are lysed by the immune system, fragments of membrane containing lipid A are released into the circulation, causing fever, diarrhea, and possible fatal endotoxic shock (also called septic shock).

Core oligosaccharide

Core oligosaccharide contains unusual sugar
Sugar

Sugar is a class of edible crystalline substances, mainly sucrose, lactose, and fructose. Human taste buds interpret its flavor as sweet. Sugar as a basic food carbohydrate primarily comes from sugar cane and from sugar beet, but also appears in fruit, honey, sorghum, sugar maple , and in many other sources....
s (e.g. KDO, keto-deoxyoctulosonate and heptose
Heptose

A heptose is a monosaccharide with seven carbon atoms.They either have an aldehyde functional group in position 1 , or a ketone functional group in position 2 ....
). The core oligosaccharide is attached to lipid A
Lipid A

Lipid A is a lipid component of an endotoxin held responsible for toxicity of Gram-negative bacteria. It is the innermost of the three regions of the lipopolysaccharide molecule, and its hydrophobe nature allows it to anchor the LPS to the outer membrane....
, 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
Antigen

An antigen is a substance that prompts the generation of antibodies and can cause an immune response. The word originated from the notion that they can stimulate antibody generation....
 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
Gram-negative

Gram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color....
 bacterial strains. The presence or absence of O chains determine whether the LPS is considered rough or smooth. Full length O-chains would render the LPS smooth while the absence or reduction of O-chains would make the LPS rough. Bacteria with rough LPS usually have more penetrable cell membranes to hydrophobic antibiotics since a rough LPS is more hydrophobic.

O side chains are easily recognized by the antibodies
Antibody

Antibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacterium and viruses....
 of the host, however, the nature of the chain can easily be modified by Gram-negative
Gram-negative

Gram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color....
 bacteria to avoid detection. The structure of the core and the O-antigen is often determined by methylation analysis or NMR
NMR

NMR may refer to:Applications of Nuclear Magnetic Resonance:* Nuclear Magnetic Resonance.* NMR Spectroscopy.* Proton NMR.* Carbon-13 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. It has recently been shown that a specific enzyme in the intestine (alkaline phosphatase
Alkaline phosphatase

Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids....
) can detoxify LPS by removing the two phosphate groups found on LPS carbohydrates . This may function as an adaptive mechanism to help the host manage potentially toxic effects of gram-negative bacteria normally found in the small intestine.

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 (e.g., in number and nature of acyl
Acyl

An acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid.. In organic chemistry, the acyl group is usually derived from a carboxylic acid of the form RCarbon Oxygen hydroxyl....
 chains even within or between genera). Some of these variations may impart antagonistic properties to these LPS. For example Rhodobacter sphaeroides
Rhodobacter sphaeroides

Rhodobacter sphaeroides is a kind of purple bacteria; a group of bacteria that can produce energy through photosynthesis.R. sphaeroides lives in deep lakes....
 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.

Lipopolysaccharide gene clusters are highly variable between different strains, subspecies, species of bacterial pathogens of plants and animals.

Immune response

LPS function has been under experimental research for several years due to its role in activating many transcription factor
Transcription factor

In the field of molecular biology, a transcription factor is a protein that binds to specific DNA sequence and thereby controls the transfer of genetic information from DNA to RNA....
s. LPS also produces many types of mediators involved in septic shock
Septic shock

Septic shock is a serious medicine condition caused by decreased tissue perfusion and oxygen delivery as a result of infection and sepsis, though the microbe may be systemic or localized to a particular site....
.

See also

  • Endotoxin
    Endotoxin

    Endotoxins are toxins associated with certain bacteria. Classically, an "endotoxin" is a toxin which, unlike an "exotoxin", is not secreted in soluble form by live bacteria, but is a structural component in the bacteria which is released mainly when bacteria are lysis....
  • Mucopolysaccharide


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