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Endotoxin
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer membrane of Gram-negative bacteria. Today, the term ''endotoxin'' is often used synonymously with LPS, although there are a few endotoxins (in the original sense of toxins that are inside the bacterial cell that are released when the cell disintegrates) that are not related to LPS, such as the so-called delta endotoxin proteins produced by ''Bacillus thuringiensis''. Lipopolysaccharides can have substantial impacts on human health, primarily through interactions with the immune system. LPS is a potent activator of the immune system and pyrogen (agent that causes fever). In severe cases, LPS can play a role in causing septic shock. In lower levels and over a longer time period, there is evidence LPS may play an important and harmful role ...
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Delta Endotoxin
Delta endotoxins (δ-endotoxins) are pore-forming toxins produced by ''Bacillus thuringiensis'' species of bacteria. They are useful for their insecticidal action and are the primary toxin produced by Bt maize/corn. During spore formation the bacteria produce crystals of such proteins (hence the name Cry toxins) that are also known as parasporal bodies, next to the endospores; as a result some members are known as a parasporin. The Cyt (cytolytic) toxin group is a group of delta-endotoxins different from the Cry group. Mechanism of action When an insect ingests these proteins, they are activated by proteolytic cleavage. The N-terminus is cleaved in all of the proteins and a C-terminal extension is cleaved in some members. Once activated, the endotoxin binds to the gut epithelium and causes cell lysis by the formation of cation-selective channels, which leads to death. For many years there was no clarity as to the relationship between aminopeptidase N and Bt toxins. Al ...
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Bacillus Thuringiensis
''Bacillus thuringiensis'' (or Bt) is a gram-positive, soil-dwelling bacterium, the most commonly used biological pesticide worldwide. ''B. thuringiensis'' also occurs naturally in the gut of caterpillars of various types of moths and butterflies, as well on leaf surfaces, aquatic environments, animal feces, insect-rich environments, and flour mills and grain-storage facilities. It has also been observed to parasitize other moths such as '' Cadra calidella''—in laboratory experiments working with ''C. calidella'', many of the moths were diseased due to this parasite. During sporulation, many Bt strains produce crystal proteins (proteinaceous inclusions), called delta endotoxins, that have insecticidal action. This has led to their use as insecticides, and more recently to genetically modified crops using Bt genes, such as Bt corn. Many crystal-producing Bt strains, though, do not have insecticidal properties. The subspecies ''israelensis'' is commonly used for control ...
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Lipid A
Lipid A is a lipid component of an endotoxin held responsible for the toxicity of gram-negative bacteria. It is the innermost of the three regions of the lipopolysaccharide (LPS), also called endotoxin molecule, and its hydrophobic nature allows it to anchor the LPS to the outer membrane. While its toxic effects can be damaging, the sensing of lipid A by the immune system may also be critical for the onset of immune responses to gram-negative infection, and for the subsequent successful fight against the infection. Chemical composition Lipid A consists of two glucosamine (carbohydrate/sugar) units, in an β(1→6) linkage, with attached acyl chains ("fatty acids"), and normally containing one phosphate group on each carbohydrate. The optimal immune activating lipid A structure is believed to contain 6 acyl chains. Four acyl chains attached directly to the glucosamine sugars are beta hydroxy acyl chains usually between 10 and 16 carbons in length. Two additional acyl chains are oft ...
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Bacterial Toxins
Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by ''Clostridium botulinum'' and less frequently by other '' Clostridium'' species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxin. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular b ...
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Virulence Factor
Virulence factors (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following: * colonization of a niche in the host (this includes movement towards and attachment to host cells) * immunoevasion, evasion of the host's immune response * immunosuppression, inhibition of the host's immune response (this includes leukocidin-mediated cell death) * entry into and exit out of cells (if the pathogen is an intracellular one) * obtain nutrition from the host Specific pathogens possess a wide array of virulence factors. Some are chromosomally encoded and intrinsic to the bacteria (e.g. capsules and endotoxin), whereas others are obtained from mobile genetic elements like plasmids and bacteriophages (e.g. some exotoxins). Virulence factors encoded on mobile genetic elements spread through horizontal gene transfer, and ...
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Septic Shock
Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defines septic shock as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by requiring a vasopressor to maintain a mean arterial pressure of 65 mm Hg or greater and having serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. The primary infection is most commonly caused by bacteria, but also may be by fungi, viruses or parasites. It may be located in any part of the body, but mos ...
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Bacterial Outer Membrane
The bacterial outer membrane is found in gram-negative bacteria. Its composition is distinct from that of the inner cytoplasmic cell membrane - among other things, the outer leaflet of the outer membrane of many gram-negative bacteria includes a complex lipopolysaccharide whose lipid portion acts as an endotoxin - and in some bacteria such as ''E. coli'' it is linked to the cell's peptidoglycan by Braun's lipoprotein. Porins can be found in this layer. Clinical significance If lipid A, part of the lipopolysaccharide, enters the circulatory system it causes a toxic reaction by activating toll like receptor TLR 4. Lipid A is very pathogenic and not immunogenic. However, the polysaccharide component is very immunogenic, but not pathogenic, causing an aggressive response by the immune system. The sufferer will have a high temperature and respiration rate and a low blood pressure. This may lead to endotoxic shock, which may be fatal. The bacterial outer membrane is physiologicall ...
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Pyrogen (fever)
Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using values between in humans. The increase in set point triggers increased muscle contractions and causes a feeling of cold or chills. This results in greater heat production and efforts to conserve heat. When the set point temperature returns to normal, a person feels hot, becomes flushed, and may begin to sweat. Rarely a fever may trigger a febrile seizure, with this being more common in young children. Fevers do not typically go higher than . A fever can be caused by many medical conditions ranging from non-serious to life-threatening. This includes viral, bacterial, and parasitic infections—such as influenza, the common cold, meningitis, urinary tract infections, appendicitis, Lassa, COVID-19, and malaria. Non-infectious causes includ ...
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Richard Friedrich Johannes Pfeiffer
Richard Friedrich Johannes Pfeiffer FRS (27 March 1858 – 15 September 1945) was a German physician and bacteriologist. Pfeiffer was born to Otto Pfeiffer, a German pastor of the local Evangelical parish, and Natalia née Jüttner, in Treustädt, Province of Posen (Prussia), and died in Bad Landeck (Prussia, now Poland). Career Pfeiffer is remembered for his many fundamental discoveries in immunology and bacteriology, particularly for the phenomenon of bacteriolysis. In 1894 he found that live cholera bacteria could be injected without ill effects into guinea pigs previously immunised against cholera, and that blood plasma from these animals added to live cholera bacteria caused them to become motionless and to lyse. This could be inhibited by previously heating the blood plasma. He called this bacteriolysis and it became known as the Pfeiffer Phenomenon, or Isayev-Pfeiffer phenomenon. Working with Robert Koch in Berlin he intellectually and experimentally conceived ...
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Exotoxins
An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface. They may exert their effect locally or produce systemic effects. Well-known exotoxins include: botulinum toxin produced by ''Clostridium botulinum''; ''Corynebacterium diphtheriae'' toxin, produced during life-threatening symptoms of diphtheria; tetanospasmin produced by ''Clostridium tetani''. The tox ...
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Gram-negative Bacteria
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic cell membrane and a bacterial outer membrane. Gram-negative bacteria are found in virtually all environments on Earth that support life. The gram-negative bacteria include the model organism '' Escherichia coli'', as well as many pathogenic bacteria, such as '' Pseudomonas aeruginosa'', '' Chlamydia trachomatis'', and '' Yersinia pestis''. They are a significant medical challenge as their outer membrane protects them from many antibiotics (including penicillin), detergents that would normally damage the inner cell membrane, and lysozyme, an antimicrobial enzyme produced by animals that forms part of the innate immune system. Additionally, the outer leaflet of this membrane comprises a compl ...
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Toxin
A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849–1919) and is derived from the word toxic. Toxins can be small molecules, peptides, or proteins that are capable of causing disease on contact with or absorption by body tissues interacting with biological macromolecules such as enzymes or cellular receptors. Toxins vary greatly in their toxicity, ranging from usually minor (such as a bee sting) to potentially fatal even at extremely low doses (such as botulinum toxin). Toxins are largely secondary metabolites, which are organic compounds that are not directly involved in an organism's growth, development, or reproduction, instead often aiding it in matters of defense. Terminology Toxins are often distinguished from other chemical agents strictly based on their biological origin. Les ...
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