Endotoxins (not to be confused with enterotoxin) are potentially toxic, natural compounds found inside pathogens such as bacteria. An enterotoxin (not to be confused with Endotoxin) is a Protein Toxin released by a Microorganism in the Intestine. Nature, in the broadest sense is equivalent to the natural world, physical universe, material world or material universe. A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have 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 lysed. A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low An exotoxin is a soluble Protein excreted by a Microrganism, including bacteria, Fungi, Algae, and Protozoa. Lysis ( Greek, lysis from lyein = to separate refers to the death of a cell by breaking of the cellular membrane often by viral or osmotic
Contents |
Lipopolysaccharide and other endotoxins
The prototypical examples of endotoxin are lipopolysaccharide (LPS) or lipo-oligo-saccharide (LOS) found in the outer membrane of various Gram-negative bacteria. Lipopolysaccharides ( LPS) are large Molecules consisting of a Lipid and a Polysaccharide joined by a Covalent bond; they are found Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol The term LPS is often used exchangeably with endotoxin, owing to its historical discovery. In the 1800s it became understood that bacteria could secrete toxins into their environment, which became broadly known as "exotoxin". An exotoxin is a soluble Protein excreted by a Microrganism, including bacteria, Fungi, Algae, and Protozoa. The term endotoxin came from the discovery that portions of Gram-negative bacteria itself can cause toxicity, hence the name endotoxin. Toxicity is the degree to which a substance is able to damage an exposed organism Studies of endotoxin over the next 50 years revealed that the effects of "endotoxin" was in fact due to lipopolysaccharide.
There are, however, endotoxins other than LPS:
- For example, delta endotoxin of Bacillus thuringiensis makes crystal-like inclusion bodies next to the endospore inside the bacteria. Bacillus thuringiensis is a Gram-positive, soil dwelling Bacterium of the Genus Bacillus. An endospore is a dormant, tough and non-reproductive structure produced by a small number of Bacteria from the Firmicute phylum It is toxic to larvae of insects feeding on plants, but is harmless to humans (as we do not possess the enzymes and receptors necessary for its processing followed by toxicity).
- The only gram positive bacteria that produces endotoxin is Listeria monocytogenes, however to be precise, they are best described as "endotoxin-like" and should not be confused with that of those found in the cell wall of gram negative bacteria, coming from the paper by Wexler & Oppenheim (1979) Infect. 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. Immunol. 23:845. Another study was carried out using GC-MS in addition to LAL test on a number of gram-neg & gram-pos (including Listeria) by Maitra et al (1986) Appl & Env Microbiology 52:510 [1]. The GC-MS results found a good correlation with LAL test in that all the gram-neg bacteria screened. Moreover, Listeria did not show any positive results with either GC-MS or LAL.
LPS consist of a polysaccharide (sugar) chain and a lipid moiety, known as lipid A, which is responsible for the toxic effects. Polysaccharides are relatively complex Carbohydrates They are Polymers made up of many Monosaccharides joined together by Glycosidic bonds The polysaccharide chain is highly variable amongst different bacteria. Endotoxins are approximately 10 kDa in size but can form large aggregates up to 1000 kDa. The unified atomic mass unit ( u) or Dalton ( Da) or sometimes universal mass unit, is an unit of Mass used to express Humans are able to produce antibodies to endotoxins after exposure but these are generally directed at the polysaccharide chain and do not protect against a wide variety of endotoxins. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Injection of a small amount of endotoxin in human volunteers produced fever, a lowering of the blood pressure, and activation of inflammation and coagulation. Endotoxins are in large part responsible for the dramatic clinical manifestations of infections with pathogenic Gram-negative bacteria, such as Neisseria meningitidis, the pathogen that causes fulminant meningitis. Neisseria meningitidis, also simply known as meningococcus, is a heterotrophic Gram-negative diplococcal Bacterium best known for Fulminant is any event or process which occurs suddenly quickly and is intense and severe to the point of lethality i Meningitis is Inflammation of the protective membranes covering the Brain and Spinal cord, known collectively as the Meninges.
Mechanism
In humans, LPS binds to the lipid binding protein (LBP) in the serum which transfers it to CD14 on the cell membrane, which in turn transfers it to another non-anchored protein, MD2, which associates with Toll-like receptor-4 (TLR4). Human beings, humans or man (Origin 1590–1600 L homō man OL hemō the earthly one (see Humus Cluster of differentiation 14 also known as CD14 is a human Gene. Toll-like receptors ( TLRs) are a class of single membrane-spanning non-catalytic receptors that recognize structurally conserved molecules derived from Microbes
CD14 and TLR4 are present in several immune system cells (including macrophages and dendritic cells), triggering the signaling cascade for macrophage/endothelial cells to secrete pro-inflammatory cytokines and Nitric oxide that lead to "endotoxic shock". An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that Dendritic cells (DCs are Immune cells and form part of the Mammalian Immune system. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the 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 Nitric oxide or nitrogen monoxide is a Chemical compound with Chemical formula N[[Oxygen O]]
Other than TLR4, components of gram negative cell wall may also activate other pathways which may contribute to the overall endotoxic effect. .
Endotoxin contamination
Endotoxins are frequent contaminants in plasmid DNA prepared from bacteria, and must be removed from the DNA to avoid unwanted inflammatory responses prior to in vivo applications such as gene therapy. A plasmid is an extra-chromosomal DNA molecule separate from the chromosomal DNA which is capable of replicating independently of the chromosomal DNA Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known In vivo ( Latin: within the living means that which takes place inside an organism. Gene therapy is the insertion of Genes into an individual's cells and tissues to treat a Disease, and Hereditary diseases in which a
In pharmaceutical production, it is necessary to remove all traces of endotoxin from drug product containers as even small amounts of endotoxin will cause illness in humans. A depyrogenation oven is used for this purpose. Depyrogenation refers to the removal of pyrogens from solution most commonly from injectable pharmaceuticals Temperatures in excess of 300 degrees Celsius are required to break down this substance. A defined endotoxin reduction rate is a correlation between time and temperature. Based on primary packaging material as syringes or vials a glass temperature of 250°C and a holding time of 30min is typical to achieve 3log reduction on endotoxin levels.
A very sensitive assay for detecting presence of endotoxin is the Limulus Amebocyte Lysate assay, utilizing blood from the Horseshoe crab. An assay is a procedure where a property or concentration of an Analyte is measured Limulus amebocyte lysate (LAL is an aqueous extract of blood cells ( Amoebocytes from the Horseshoe crab, Limulus polyphemus. The horseshoe crab or Atlantic horseshoe crab ( Limulus polyphemus) is a marine Chelicerate Arthropod. Very low levels of LPS can cause coagulation of the limulus lysate due to a powerful amplification through an enzymatic cascade.
Endotoxemia
The presence of endotoxins in the blood is called Endotoxemia. It can lead to septic shock, if the immune response is severely pronounced.
See also
References
- Textbook of Bacteriology
- Sofer, G. A bioaerosol is a biological Aerosol. These particles are very small and range in size from less than one micrometer (0 An exotoxin is a soluble Protein excreted by a Microrganism, including bacteria, Fungi, Algae, and Protozoa. Depyrogenation refers to the removal of pyrogens from solution most commonly from injectable pharmaceuticals ; Hagel, L. (1997). Handbook of Process Chromatography: A guide to Optimization, Scale-up, and Validation. Academic Press, 158-161. ISBN 0-12-654266-X
External links
Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and booksDictionary
endotoxin
-noun
- Any toxin secreted by a microorganism and released into the surrounding environment only when it dies
Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic