Lipopolysaccharide (LPS) is a large molecule consisting of a lipid and a polysaccharide (carbohydrate) joined by a covalent bond. In Chemistry, a molecule is defined as a sufficiently stable electrically neutral group of at least two Atoms in a definite arrangement held together by Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble Polysaccharides are relatively complex Carbohydrates They are Polymers made up of many Monosaccharides joined together by Glycosidic bonds Carbohydrates (from ' Hydrates of Carbon ' or saccharides ( Greek σάκχαρον meaning " Sugar " are the most
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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. The outer membrane refers to the outside membranes of Gram-negative bacteria, the Chloroplast, or the Mitochondria. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol LPS is an endotoxin, and induces a strong response from normal animal immune systems. Endotoxins (not to be confused with Enterotoxin) are potentially toxic, natural compounds found inside Pathogens such as Bacteria. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor The only Gram-positive bacteria that possesses LPS is Listeria monocytogenes, the common infective agent in unpasteurized milk. Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. Listeria monocytogenes is a Gram-positive Bacterium, in the division Firmicutes, named for Joseph Lister. Pasteurization is the process of heating Liquids for the purpose of destroying bacteria, Protozoa, Molds and Yeasts The process was Milk is an opaque white liquid produced by the Mammary glands of female Mammals (including Monotremes. [1]
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. Endotoxins (not to be confused with Enterotoxin) are potentially toxic, natural compounds found inside Pathogens such as Bacteria. The cluster of differentiation (often abbreviated as CD) is a protocol used for the identification and investigation of Cell surface molecules present on Leukocytes Toll-like receptor 4, also known as TLR4, is a human Gene. TLR 4 is a Toll-like receptor. Lymphocyte antigen 96, also known as LY96, is a human Gene. The Protein encoded by this gene is involved in binding Lipopolysaccharide with In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular 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. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer
LPS is additionally an exogenous pyrogen (external fever-inducing compound).
With the Lipopolysaccharide being of crucial importance to gram negative bacterial cells, reslting in the death of the cell if it mutated or removed, it is therefore a prime target for future antimicrobial substances.
Composition
It comprises three parts:
- polysaccharide (O) side chains
- core polysaccharide (core oligosaccharide in genus Neisseria)
- lipid A
Lipid A
Lipid A contains unusual fatty acids ('e. Polysaccharides are relatively complex Carbohydrates They are Polymers made up of many Monosaccharides joined together by Glycosidic bonds A side chain in Organic chemistry and Biochemistry is a part of a Molecule that is attached to a core structure Lipid A is a Lipid component of an Endotoxin held responsible for Toxicity of Gram-negative Bacteria. In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which g. ' hydroxy-myristic acid) and is embedded into the outer membrane while the rest of the LPS projects from the surface. Myristic acid, also called tetradecanoic acid, is a common saturated Fatty acid with the molecular formula CH3(CH212COOH This is the key in the toxicity.
Core oligosaccharide
Core oligosaccharide contains unusual sugars (e. Sugar is a class of edible Crystalline substances mainly Sucrose, Lactose, and Fructose. g. KDO, keto-deoxyoctulosonate and heptose). A heptose is a Monosaccharide with seven Carbon atoms They either have an Aldehyde Functional group in position 1 ( aldoheptoses
The core oligosaccharide is attached to lipid A, which is also in part responsible for the toxicity of gram-negative bacteria. Lipid A is a Lipid component of an Endotoxin held responsible for Toxicity of Gram-negative Bacteria.
O-antigen
The polysaccharide side chain is referred to as the O-antigen of the bacteria. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response O side chain (O-antigen) is also a polysaccharide chain that extends from the core polysaccharide. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response The composition of the O side chain varies between different gram-negative bacterial strains. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol 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. [2]Bacteria with rough LPS usually have more penetrable cell membranes to hydrophobic antibiotics since a rough LPS is more hydrophobic. [3]
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. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have 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. It has recently been shown that a specific enzyme in the intestine (alkaline phosphatase) can detoxify LPS by removing the two phosphate groups found on LPS carbohydrates [4]. Alkaline phosphatase ( ALP) ( is a Hydrolase Enzyme responsible for removing Phosphate groups from many types of molecules including 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 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. Rhodobacter sphaeroides is a kind of Purple bacteria; a group of bacteria that can produce energy through Photosynthesis.
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. TLR-2 is a Biomolecule, which plays a role in the human Immune system. [5][6]
Functions
LPS function has been under experimental research for several years due to its role in activating many transcription factors. In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences LPS also produces many types of mediators involved in septic shock. Septic shock is a very serious medical condition caused by decreased tissue perfusion and oxygen delivery as a result of Infection and Sepsis, though the
Diversity
Lipololysaccharide gene clusters are highly variable between different strains, subspecies, species of bacterial pathogens of plants and animals. [7][8]
References
- ^ Wexler, Hannah; Joel D. Oppenheim (March 1979). "Isolation, Characterization, and Biological Properties of an Endotoxin-Like Material from the Gram-Positive Organism Listeria monocytogenes" (PDF). Infection and Immunity 23 (3): 845-857. American Society for Microbiology. ISSN 0019-9567. An International Standard Serial Number ( ISSN) is a unique eight-digit number used to identify a print or electronic Periodical publication. PMID 110684.
- ^ Rittig MG et al (2004). "Smooth and rough lipopolysaccharide phenotypes of Brucella induce different intracellular trafficking and cytokine/chemokine release in human monocytes". Journal of Leukocyte Biology 5 (4): 196-200. PMID 12960272.
- ^ Tsujimoto H et al (2003). "Diffusion of macrolide antibiotics through the outer membrane of Moraxella catarrhalis". Journal of Infection and Chemotherapy 74: 1045-1055. PMID 11810516.
- ^ Bates J. M. et al (2007). "Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. ". Cell Host and Microbe 2(6): 371-382. PMID 18078689.
- ^ Netea M et al (2002). "Does the shape of lipid A determine the interaction of LPS with Toll-like receptors?". Trends Immunol 23 (3): 135-9. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11864841.
- ^ Seydel U, Oikawa M, Fukase K, Kusumoto S, Brandenburg K (2000). "Intrinsic conformation of lipid A is responsible for agonistic and antagonistic activity". Eur J Biochem 267 (10): 3032-9. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10806403.
- ^ Reeves P, Wang L (2002). "Genomic organization of LPS-specific loci". Curr Top Microbiol Immunol 264 (1): 109-35. PMID 12014174.
- ^ Patil P, Sonti R (2004). "Variation suggestive of horizontal gene transfer at a lipopolysaccharide (lps) biosynthetic locus in Xanthomonas oryzae pv. oryzae, the bacterial leaf blight pathogen of rice". BMC Microbiol 4 (1): 40. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15473911.
See also
External links
Endotoxins (not to be confused with Enterotoxin) are potentially toxic, natural compounds found inside Pathogens such as Bacteria. Glycosaminoglycans (GAGs or mucopolysaccharides are long unbranched Polysaccharides consisting of a repeating Disaccharide unit Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and booksDictionary
lipopolysaccharide
-noun
- (biochemistry) Any of a large class of lipids conjugated with polysaccharides
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