Microbial toxins
Encyclopedia
Microbial toxins are toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

s produced by microorganisms, including bacteria, viruses and fungi. Microbial toxins are important virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

 determinants responsible for microbial pathogenicity
Pathogenicity
Pathogenicity is the ability of a pathogen to produce an infectious disease in an organism.It is often used interchangeably with the term "virulence", although virulence is used more specifically to describe the relative degree of damage done by a pathogen, or the degree of pathogenicity caused by...

 and/or evasion of the host immune response. Some bacterial toxins, such as Botulinum neurotoxins, are the most potent natural toxins known. However, microbial toxins also have important uses in medical science and research. Potential applications of toxin research include combating microbial virulence, the development of novel anti-cancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.'

Botulinum neurotoxin

Botulinum neurotoxins (BoNTs) are the most potent natural toxins known. The family of BoNTs comprises seven antigenically distinct serotype
Serotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...

s (A to G) that are produced by various toxigenic strains of spore-forming anaerobic Clostridium botulinum
Clostridium botulinum
Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...

. They act as metalloproteinase
Metalloproteinase
Metalloproteinases constitute a family of enzymes from the group of proteases, classified by the nature of the most prominent functional group in their active site. These are proteolytic enzymes whose catalytic mechanism involves a metal. Most metalloproteases are zinc-dependent, but some use...

s that enter peripheral cholinergic nerve terminals and cleave proteins that are crucial components of the neuroexocytosis apparatus, causing a persistent but reversible inhibition of neurotransmitter release resulting in flaccid muscle paralysis. They are the causative agent of the deadly food poisoning disease, botulism, and could pose a major biological warfare threat due to their extreme toxicity and ease of production. They also serve as powerful tools to treat an ever expanding list of medical conditions.

Tetanus toxin

Clostridium tetani
Clostridium tetani
Clostridium tetani is a rod-shaped, anaerobic bacterium of the genus Clostridium. Like other Clostridium species, it is Gram-positive, and its appearance on a gram stain resembles tennis rackets or drumsticks. C. tetani is found as spores in soil or in the gastrointestinal tract of animals. C...

produces tetanus toxin (TeNT protein) which leads to a fatal condition known as tetanus
Tetanus
Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...

 in many vertebrates (including humans) and invertebrates.

Anthrax toxin

Bacillus anthracis
Bacillus anthracis
Bacillus anthracis is the pathogen of the Anthrax acute disease. It is a Gram-positive, spore-forming, rod-shaped bacterium, with a width of 1-1.2µm and a length of 3-5µm. It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions.It is one of few bacteria known to...

produces two major virulence factors, a tripartite exotoxin
Exotoxin
An exotoxin is a toxin excreted by a microorganism, like bacteria, fungi, algae, and protozoa. 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...

 referred to as anthrax
Anthrax
Anthrax is an acute disease caused by the bacterium Bacillus anthracis. Most forms of the disease are lethal, and it affects both humans and other animals...

 toxin, and an antiphagocytic capsule. These virulence factors mediate pathogen survival and, in the case of toxin, directly induce damage to the host. Two distinct enzymatic activities are associated with anthrax toxin, each encoded by a separate protein. The enzymatic subunits are lethal factor (LF), a zinc-dependent metalloproteinase, and oedema factor (EF), a calcium- and calmodulin-dependent adenylate cyclase. LF and EF gain access to the host cytosol by binding to and translocating through a pore formed by the shared binding subunit, protective antigen (PA). The combination of LF and PA is called lethal toxin (LT), and this toxin inactivates MAPK/ERK pathway
MAPK/ERK pathway
The MAPK/ERK pathway is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a growth factor binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a...

 in the host. Edema toxin (ET), formed by the combination of EF and PA, produces high cAMP levels in host cells. Early during infection, systemic toxin levels are low, and likely modulate the host immune response locally, thereby allowing for establishment of infection. Late in infection, toxin concentrations increase causing organ damage, vascular leakage, and ultimately death of the host.

Subtilase cytotoxin

Subtilase
Subtilase
Subtilases are a family of subtilisin-like serine proteases. They appear to have independently and convergently evolved an Asp/Ser/His catalytic triad, like in the trypsin serine proteases...

 cytotoxin (SubAB) is the recently-recognised prototype of a new AB5 toxin family secreted by Shiga toxigenic Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

(STEC). Its A subunit is a subtilase-like serine protease and cytotoxicity for eukaryotic cells is due to a highly specific, single-site cleavage of BiP/GRP78, an essential Hsp70 family chaperone located in the ER. This cleavage triggers a severe ER stress response, ultimately resulting in apoptosis. The B subunit has specificity for glycans terminating in the sialic acid N-glycolylneuraminic acid. The role of SubAB in human disease remains to be established.

Pasteurella multocida toxin

Pasteurella multocida
Pasteurella multocida
Pasteurella multocida is a Gram-negative, non-motile coccobacillus that is penicillin-sensitive and belongs to the Pasteurellaceae family . It can cause avian cholera in birds and a zoonotic infection in humans, which typically is a result of bites or scratches from domestic pets...

toxin (PMT) is the major pathogenic deteriment of Pasteurella multocida. The species P. multocida causes various diseases of animals and humans. The toxin is the causative agent of the economically important atrophic rhinitis
Rhinitis
Rhinitis , commonly known as a stuffy nose, is the medical term describing irritation and inflammation of some internal areas of the nose. The primary symptom of rhinitis is nasal dripping. It is caused by chronic or acute inflammation of the mucous membrane of the nose due to viruses, bacteria or...

 in swine. Stimulation of several signalling pathways is induced by PMT. Most remarkable is a potent mitogenic effect. Phospholipase Cβ and the small GTPase Rho are activated due to stimulation of heterotrimeric G proteins of the Gαq and Gα12/13 family.

Vibrio RTX toxins

Multifunctional-Autoprocessing RTX toxin
RTX toxin
The RTX toxin family is a group of exotoxins produced by gram-negative bacteria. All RTX toxins share a common gene organization and structural appearance. Gram-negative bacteria secrete the toxins into the extracellular space using the type I secretion system. RTX is an abbreviation of "repeats...

s are a unique family of secreted proteins toxins, predominantly produced by the Vibrio
Vibrio
Vibrio is a genus of Gram-negative bacteria possessing a curved rod shape, several species of which can cause foodborne infection, usually associated with eating undercooked seafood. Typically found in saltwater, Vibrio are facultative anaerobes that test positive for oxidase and do not form...

sp. The best characterized of these toxins is produced by V. cholerae. In the eukaryotic cell, this toxin has three distinct biochemical activities resulting in autoprocessing, covalent crosslinking of actin, and inactivation of Rho-family GTPases, ultimately resulting in destruction of the actin cytoskeleton. Related toxins produced by V. vulnificus and V. anguillarum have some similar mechanisms of action. These toxins may assist the bacterium to evade host immune defenses.

Helicobacter pylori toxin

Helicobacter pylori
Helicobacter pylori
Helicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...

, a Gram-negative bacterium that colonizes the human stomach, secretes a toxin known as VacA. This toxin was initially identified based on its ability to cause vacuolation in cultured gastric epithelial cells. VacA causes several other alterations in gastric epithelial cells and targets multiple types of immune cells. Most VacA-induced cellular alterations are attributable to insertion of the toxin into cellular membranes and the formation of membrane channels.

Staphylococcal toxins

Immune evasion proteins from Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...

have a significant conservation of protein structures and a range of activities that are all directed at the two key elements of host immunity, complement and neutrophils. These secreted virulence factors assist the bacterium in surviving immune response mechanisms.

Cyanobacteria toxins

Cyanobacteria produce a large variety of bioactive compounds, including substances with anti-cancer and anti-viral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxin
Hepatotoxin
A hepatotoxin is a toxic chemical substance that damages the liver.It can be a side-effect of medication, or found naturally, as microcystins, or in laboratory environments....

s and neurotoxin
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...

s.

Mycotoxins

In agriculture, Aspergillus originally was considered a serious problem largely because of its prevalence in the biodeterioration
Microbial biodegradation
Interest in the microbial biodegradation of pollutants has intensified in recent years as humanity strives to find sustainable ways to clean up contaminated environments...

 of stored crops and as an opportunistic pathogen of field crops, particularly under high moisture conditions. During the early 1960s, the discovery of aflatoxins associated with massive deaths of poultry, trout and other domesticated animals species worldwide raised new awareness that these fungi posed threats to foods and feeds beyond their ability to rot plant materials. Research on aflatoxins led to a so-called 'golden age' of mycotoxin research during which many new fungal toxins were discovered from species of Aspergillus and other common moulds. In addition to aflatoxins, other important Aspergillus mycotoxins include ochratoxin, patulin and fumigillin.

Aflatoxins are still recognized as the most important mycotoxins. They are synthesized by only a few Aspergillus species of which A. flavus and A. parasiticus are the most problematic. The expression of aflatoxin-related diseases is influenced by factors such as age, nutrition, sex, species and the possibility of concurrent exposure to other toxins. The main target organ in mammals is the liver so aflatoxicosis is primarily a hepatic disease. Conditions increasing the likelihood of aflatoxicosis in humans include limited availability of food, environmental conditions that favour mould growth on foodstuffs, and lack of regulatory systems for aflatoxin monitoring and control.

A. flavus and A. parasiticus are weedy moulds that grow on a large number of substrates, particularly under high moisture conditions. Aflatoxins have been isolated from all major cereal crops, and from sources as diverse as peanut butter and marijuana. The staple commodities regularly contaminated with aflatoxins include cassava, chillies, corn, cotton seed, millet, peanuts, rice, sorghum, sunflower seeds, tree nuts, wheat, and a variety of spices intended for human or animal food use. When processed, aflatoxins get into the general food supply where they have been found in both pet and human foods as well as in feedstocks for agricultural animals. Aflatoxin transformation products are sometimes found in eggs, milk products and meat when animals are fed contaminated grains.

Human exposure to aflatoxins is difficult to avoid because A. flavus grows aggressively in many foods at all stages of the food chain: in the field, in storage and in the home. Evidence for acute human aflatoxicosis has been reported from several underdeveloped countries such as India and Thailand. The symptoms of severe aflatoxicosis include oedema, hemorrhagic necrosis of the liver and profound lethargy. Further, aflatoxins are potent carcinogens, especially aflatoxin B1. Based on epidemiological studies done in Asian and Africa, in 1988 the International Agency for Research on Cancer, part of the World Health Organization, placed aflatoxin B1 on the list of human carcinogens. In developed countries, the emphasis on keeping aflatoxin out of the food chain concerns its carcinogenic potential. Strong regulatory limits (4-30 ppb) have been established for many commodities.

Fungal ribotoxins

Ribotoxins are a family of fungal extracellular ribonuclease
Ribonuclease
Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...

s which inactivate ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

s by specifically cleaving a single phosphodiester bond located at the universally conserved sarcin/ricin loop of the large rRNA. The subsequent inhibition of protein biosynthesis is followed by cell death via apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

. Ribotoxins are also able to interact with membranes containing acid phospholipids, their cytotoxicity being preferentially directed towards cells showing altered membrane permeability, e.g. transformed or virus infected cells.

See also

  • Alpha toxin
    Alpha toxin
    Alpha Toxin or alpha-toxin refers to several different protein toxins produced by bacteria. Alpha toxin may be:*Staphylococcus aureus alpha toxin, a membrane-disrupting toxin that creates pores causing hemolysis and tissue damage....

  • Anthrax toxin
    Anthrax toxin
    Anthrax toxin is a three-protein exotoxin secreted by virulent strains of the bacterium, Bacillus anthracis--the causative agent of anthrax. The toxin was first discovered by Harry Smith in 1954. Anthrax toxin is composed of a cell-binding protein, known as protective antigen , and two enzyme...

  • Bacterial toxin
    Bacterial toxin
    A bacterial toxin is a type of toxin that is generated by bacteria.Toxinosis is pathogenesis caused by the bacterial toxin alone, not necessarily involving bacterial infection A bacterial toxin is a type of toxin that is generated by bacteria.Toxinosis is pathogenesis caused by the bacterial toxin...

  • Botulinum toxin
    Botulinum toxin
    Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...

  • Cholera toxin
    Cholera toxin
    Cholera toxin is a protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the massive, watery diarrhea characteristic of cholera infection.- Structure :...

  • Cyanotoxin
    Cyanotoxin
    Cyanotoxins are toxins produced by bacteria called cyanobacteria . Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under certain conditions, they reproduce exponentially to form blooms. Blooming cyanobacteria can produce cyanotoxins in such...

  • Diphtheria toxin
    Diphtheria toxin
    Diphtheria toxin is an exotoxin secreted by Corynebacterium diphtheriae, the pathogen bacterium that causes diphtheria. Unusually, the toxin gene is encoded by a bacteriophage...

  • Exotoxin
    Exotoxin
    An exotoxin is a toxin excreted by a microorganism, like bacteria, fungi, algae, and protozoa. 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...

  • Food microbiology
    Food microbiology
    Food microbiology is the study of the microorganisms that inhabit, create, or contaminate food. Of major importance is the study of microorganisms causing food spoilage. "Good" bacteria, however, such as probiotics, are becoming increasingly important in food science...

  • Microbiology
    Microbiology
    Microbiology is the study of microorganisms, which are defined as any microscopic organism that comprises either a single cell , cell clusters or no cell at all . This includes eukaryotes, such as fungi and protists, and prokaryotes...

  • Neurotoxin
    Neurotoxin
    A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...

  • Pertussis toxin
    Pertussis toxin
    Pertussis toxin is a protein-based AB5-type exotoxin produced by the bacterium Bordetella pertussis, which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection...

  • Shiga toxin
    Shiga toxin
    Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, whose genes are considered to be part of the genome of lambdoid prophages. The toxins are named for Kiyoshi Shiga, who first described the bacterial origin of dysentery caused by Shigella dysenteriae. The most common...

  • Shiga-like toxin
    Shiga-like toxin
    Shiga-like toxin, also known as verotoxin, is a toxin generated by some strains of Escherichia coli . It is named for its similarity to the AB5-type Shiga toxin produced by the bacteria Shigella dysenteriae....

  • Toxin
    Toxin
    A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

  • Toxin-antitoxin system
    Toxin-antitoxin system
    A toxin-antitoxin system is a set of two or more closely linked genes that together encode both a protein 'poison' and a corresponding 'antidote'. When these systems are contained on plasmids – transferable genetic elements – they ensure that only the daughter cells that inherit the plasmid...

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