Microbial toxins are
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– ...
s produced by
micro-organisms
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
, including
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
,
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
,
protozoa
Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
,
dinoflagellates
The dinoflagellates (Greek δῖνος ''dinos'' "whirling" and Latin ''flagellum'' "whip, scourge") are a monophyletic group of single-celled eukaryotes constituting the phylum Dinoflagellata and are usually considered algae. Dinoflagellates are ...
, and
viruses
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
. 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
Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromusc ...
, which is primarily produced by ''
Clostridium botulinum
''Clostridium botulinum'' is a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum.
The botulinum toxin can cause botulism, a severe flaccid paralytic disease in humans an ...
'' and less frequently by other ''
Clostridium
''Clostridium'' is a genus of anaerobic, Gram-positive bacteria. Species of ''Clostridium'' inhabit soils and the intestinal tract of animals, including humans. This genus includes several significant human pathogens, including the causative ag ...
'' 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
Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...
and
cellular biology
Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...
.
Bacterial
Bacteria toxins which can be classified as either
exotoxin
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, simi ...
s or
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 ...
s. Exotoxins are generated and actively secreted; endotoxins remain part of the bacteria. Usually, an endotoxin is part of the
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 ...
, and it is not released until the bacterium is killed by the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
. The body's response to an endotoxin can involve severe
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
. In general, the inflammation process is usually considered beneficial to the infected host, but if the reaction is severe enough, it can lead to
sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
. Exotoxins are typically proteins with enzymatic activity that interfere with host cells triggering the symptoms associated with the disease. Exotoxins are also relatively specific to the bacteria that produce it; for example, diphtheria toxin is only produced by Corynebacterium diphtheriae bacteria and is required for the diphtheria disease.
Some bacterial toxins can be used in the treatment of
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s. Endotoxins most commonly refer to the
lipopolysaccharide
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 m ...
(LPS) or
lipooligosaccharide
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 me ...
(LOS) that are in the outer plasma membrane of Gram-negative bacteria. Exotoxins are typically proteins with enzymatic activity that interfere with host cells triggering the symptoms associated with the disease. Exotoxins are also relatively specific to the bacteria that produce it; for example, diphtheria toxin is only produced by Corynebacterium diphtheriae bacteria and is required for the diphtheria disease. Not all strains of a bacteria species are virulent; there are some strains of Corynebacterium diphtheriae that do not produce diphtheria toxin and are considered nonvirulent and nontoxigenic. Additional classifications used to describe toxins include
enterotoxin
An enterotoxin is a protein exotoxin released by a microorganism that targets the intestines.
Enterotoxins are chromosomally encoded or plasmid encoded exotoxins that are produced and secreted from several bacterial organisms. They are heat labi ...
,
neurotoxin
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
,
leukocidin
A leukocidin is a type of cytotoxin created by some types of bacteria (''Staphylococcus''). It is a type of pore-forming toxin. The model for pore formation is step-wise. First, the cytotoxin’s “S” subunit recognizes specific protein-containi ...
or
hemolysin
Hemolysins or haemolysins are lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. Although the lytic activity of some microbe-derived hemolysins on red blood cells may be of great importance for nutrient acqu ...
which indicate where in the host’s body the toxin targets. . Enterotoxins target the intestines, neurotoxins target neurons, leukocidin target leukocytes (white blood cells), and hemolysins target red blood cells. Exotoxin activity can be separated into specific cytotoxic activity or broad cytotoxic activity based on whether the toxin targets specific cell types or various cell types and tissues, respectively. Lethal toxins refers to the group of toxins that are the obvious agents responsible for death associated with the infection.
Toxinosis is pathogenesis caused by the bacterial toxin alone, not necessarily involving
bacterial infection
Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often beneficial but others can cause infectious diseases. The number of ...
(e.g. when the bacteria have died, but have already produced toxin, which are ingested). It can be caused by ''
Staphylococcus aureus
''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...
'' toxins, for example.
Examples
Clostridial
There are over 200
Clostridium
''Clostridium'' is a genus of anaerobic, Gram-positive bacteria. Species of ''Clostridium'' inhabit soils and the intestinal tract of animals, including humans. This genus includes several significant human pathogens, including the causative ag ...
species in the world that live in mundane places such as soil, water, dust, and even our digestive tracts. Some of these species produce harmful toxins such as botulinum toxin and tetanus toxin among others. Most clostridium species that do have toxins typically have binary toxins with the first unit involved in getting the toxin into the cell and the second unit cause cellular stress or deformation. Clostridial toxins are widespread and aid in the production of many diseases in humans and other organisms. Clostridial toxins are known to aid in gastrointestinal diseases and there is a wide range of mechanisms that clostridial toxins take to invade or enter the cell of the host. Pore forming bacterial toxins are common and have a very interesting way of entering or invading the host's cell. The mechanism that clostridial toxins follow includes clostridia forming pores and then the pores inserting themselves into the cell membrane of cells. Clostridial toxins have the ability to damage or alter the cell membrane damaging the extracellular matrix of the organism.
Toxin A and
toxin B are two toxins produced by ''Clostridium difficile''. Toxin A and toxin B are
glycosyltransferase
Glycosyltransferases (GTFs, Gtfs) are enzymes ( EC 2.4) that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar (also known as the "glycosyl donor") to a nucleophilic glycos ...
s that cause the antibiotic-associated pseudomembranous colitis and severe diarrhea that characterize disease presentation of
''C. diff'' infections.
= ''Botulinum''
=
''Botulinum'' neurotoxins (BoNTs) are the causative agents 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 that benefit from its paralytic properties, an example drug with BoNTs as the active ingredient is Botox.
They also serve as powerful tools to treat an ever expanding list of medical conditions that benefit from its paralytic properties delivered through localized injections, an example drug with BoNTs as the active ingredient is Botox. Botulinum neurotoxins (BoNTs) are protein neurotoxins that are produced by the bacteria Clostridium. BoNTs are now largely being studied due to their ability to aid in chronic inflammatory diseases such as acne, multiple sclerosis, and for cosmetic purposes
= Tetanus
=
''
Clostridium tetani
''Clostridium tetani'' is a common soil bacterium and the causative agent of tetanus. Vegetative cells of ''Clostridium tetani'' are usually rod-shaped and up to 2.5 μm long, but they become enlarged and tennis racket- or drumstick-shaped when ...
'' produces tetanus toxin (TeNT protein), which leads to a fatal condition known as
tetanus
Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
in many vertebrates (including humans) and invertebrates. While tetanus toxin is produced from ''Clostridium tetani'', a spore forming bacteria found in soil, Tetanus is a paralytic disease that is global and commonly affects newborns as well as non-immunized individuals. Tetanus enters the body of organisms through wounds or skin breaks and can be found in manure, soil, and dust. Tetanus mechanism includes tetanus preventing the transmission of glycine and γ-aminobutyric acid from inhibitory interneurons in the spinal cord, leading to spastic paralysis. Glycine is an important amino acid that is essential for adequate nervous system function aiding in cell communication throughout the body. When tetanus toxin enters the body it is taken up by cholinergic nerve endings traveling axonally into the brain and spinal cord, disrupting motor function in individuals. Although tetanus is a damaging toxin that has a multitude of symptoms it can be prevented through vaccination.
Perfringolysin O toxin
''Clostridium perfringens'' is an anaerobic, gram-positive bacteria that is often found in the large and small intestines of humans and other animals. ''Clostridium perfringens'' has the ability to reproduce quickly producing toxins relating to the cause of diseases. The pore-forming toxin perfringolysin has the ability to cause gangrene in calves with the presence of alpha toxin.
Staphylococcal
Immune evasion proteins from ''
Staphylococcus aureus
''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...
'' 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.
Examples of toxins produced by strains of ''S. aureus'' include enterotoxins that cause food-poisoning, exfoliative toxins that cause
scalded skin syndrome, and
toxic-shock syndrome toxin (TSST) that underlies
toxic shock syndrome
Toxic shock syndrome (TSS) is a condition caused by bacterial toxins. Symptoms may include fever, rash, skin peeling, and low blood pressure. There may also be symptoms related to the specific underlying infection such as mastitis, osteomyeliti ...
.
These toxin examples are classified as
superantigen
Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically it causes non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. SAgs are p ...
s.
Multi-drug resistant ''S. aureus'' strains also produce alpha toxin, classified as a
pore-forming toxin
Pore-forming proteins (PFTs, also known as pore-forming toxins) are usually produced by bacteria, and include a number of protein exotoxins but may also be produced by other organisms such as apple snails that produce perivitellin-2 or earthwor ...
, which can cause
abscess
An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends b ...
es.
Shiga
Shiga toxin
Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial orig ...
s (Stxs), responsible for foodborne illnesses, are a classification of toxins produced by
Shiga toxin-producing ''Escherichia coli'' (STEC) and ''
Shigella dysenteriae
''Shigella dysenteriae'' is a species of the rod-shaped bacterial genus ''Shigella''. ''Shigella'' species can cause shigellosis ( bacillary dysentery). Shigellae are Gram-negative, non-spore-forming, facultatively anaerobic, nonmotile bacteri ...
'' serotype 1. Stx was first identified in ''S. dysenteriae'' and was later found to be produced by certain strains of ''E. coli''.
Stxs act through inhibiting protein synthesis of infected cells and can be divided into two antigenically different groups: Stx/Stx1 and Stx2.
Stx1 is immunologically equivalent to Stx; however, it received a separate name to distinguish that it's produced by STEC not ''S. dysenteriae''. Stx2 is produced only by STEC and is antigenically different from Stx/Stx1. The term shiga-like toxins was previously used to further distinguish the shiga toxins produced by ''E. coli,'' but nowadays, they are collectively referred to as shiga toxins.
Within the STEC strains, a subgroup classified as enterohemorrhagic ''E. coli'' (EHEC) represent a class of pathogens with more severe virulence factors in addition to the ability to produce Stxs. EHEC infections result in more severe diseases of hemorrhagic colitis and
hemolytic uremic syndrome
Hemolysis or haemolysis (), also known by several other names, is the rupturing ( lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo ...
.
There are around 200 strains of STEC, and the wide range of diversity and virulence between them can be partly attributed to phage-mediated horizontal transfer of genetic material.
Anthrax toxin
Anthrax
Anthrax is an infection caused by the bacterium ''Bacillus anthracis''. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The sk ...
disease in humans results from infection with toxin producing ''
Bacillus anthracis
''Bacillus anthracis'' is a gram-positive and rod-shaped bacterium that causes anthrax, a deadly disease to livestock and, occasionally, to humans. It is the only permanent ( obligate) pathogen within the genus ''Bacillus''. Its infection is a ...
'' strains that can be inhaled, ingested in contaminated food or drink, or obtained through breaks in the skin like cuts or scrapes.
Domestic and wild animals can also be infected via inhalation or ingestion. Depending on the route of entry, disease can present initially as inhalation anthrax, cutaneous anthrax, or gastrointestinal anthrax, but eventually will spread throughout the body, resulting in death, if not treated with antibiotics.
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 ...
is composed of three domains: protective antigen (PA), edema factor (EF), and lethal factor (LF). EF is an adenylate cyclase that targets ATP. LF enzyme is a metalloprotease that confers the lethal phenotype associated with anthrax disease.
As LF is the agent responsible for the death of infected hosts, it is classified in the group of lethal toxins.
Diphtheria toxin
Diphtheria toxin
Diphtheria toxin is an exotoxin secreted by '' Corynebacterium diphtheriae'', the pathogenic bacterium that causes diphtheria. The toxin gene is encoded by a prophageA prophage is a virus that has inserted itself into the genome of the host ...
is produced by virulent ''
Corynebacterium diphtheriae
''Corynebacterium diphtheriae'' is the pathogenic bacterium that causes diphtheria. It is also known as the Klebs–Löffler bacillus, because it was discovered in 1884 by German bacteriologists Edwin Klebs (1834–1912) and Friedrich Löffl ...
'' that infect the mucosal membranes of the throat and nasal cavity causing a gray, thickened lining of the throat, sore throat, weakness, mild fever, swollen glands of the neck, and difficulty breathing.
Diphtheria toxin is an ADP-ribosyltransferase that inhibits protein synthesis which causes the symptoms associated with the disease.
Diphtheria
Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
used to be a leading cause of childhood death until the creation of a vaccine.
The
diphtheria vaccine
Diphtheria vaccine is a toxoid vaccine against diphtheria, an illness caused by '' Corynebacterium diphtheriae''. Its use has resulted in a more than 90% decrease in number of cases globally between 1980 and 2000. The first dose is recommended ...
contains a diphtheria toxoid, antigenically identical yet inactivated and non-toxic. When the toxoid is introduced to the body in a vaccine, an immune response is mounted without sequelae associated with the toxigenicity.
Pertussis toxin
Pertussis toxin
Pertussis toxin (PT) 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. Res ...
is produced by virulent ''
Bordetella pertussis
''Bordetella pertussis'' is a Gram-negative, aerobic, pathogenic, encapsulated coccobacillus of the genus ''Bordetella'', and the causative agent of pertussis or whooping cough. Like '' B. bronchiseptica'', ''B. pertussis'' is motile and expres ...
'' and is responsible for the disease of whooping cough, a respiratory disease that can be fatal for infants. The severe, uncontrollable coughing makes it difficult to breathe causing the “whooping” sound that occurs with inhalation. Bordetella pertussis targets cilia of the upper respiratory tract which are damaged by the Pertussis toxin, an ADP-ribosyltransferase that targets G-proteins.
Cholera toxin
Cholera
Cholera is an infection of the small intestine by some strains of the bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting and ...
, characterized by copious watery diarrhea, is a potentially life-threatening illness transmitted through the fecal-oral route via food or water contaminated with toxigenic ''
Vibrio cholerae
''Vibrio cholerae'' is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and oth ...
''. ''V. cholerae'' targets the intestines and secretes
cholera toxin
Cholera toxin (also known as choleragen and sometimes abbreviated to CTX, Ctx or CT) is AB5 multimeric protein complex secreted by the bacterium ''Vibrio cholerae''. CTX is responsible for the massive, watery diarrhea characteristic of cholera ...
, an exotoxin and potent enterotoxin that acts as an ADP-ribosyltransferase targeting G-proteins.
This causes an increase in intracellular cAMP and forces intestinal cells to expel significant amounts of water and electrolytes into the lumen.
Listeriolysin O toxin
Listeriolysin O toxin is an exotoxin produced by ''
Listeria monocytogenes
''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host' ...
'' and is associated with foodborne systemic illness and
meningitis
Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
.
Listeriolysin O toxin is classified as a pore-forming toxin that targets host cholesterol cells, inserting a pore into the host cell plasma membrane and permanently disabling cellular functioning.
Lipopolysaccharides (LPS)
Lipopolysaccharide
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 m ...
s (LPS) produced by gram-negative bacteria are an example of endotoxins. LSP are structural components of the bacteria's outer membrane that only become toxic to the host as a result of the immune system's destruction of the bacteria cell membrane.
Detection methods in fresh water environments
The most prominent natural
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– ...
groups that exist in aquatic environments are
mycotoxin
A mycotoxin (from the Greek μύκης , "fungus" and τοξίνη , "toxin") is a toxic secondary metabolite produced by organisms of kingdom Fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' ...
s,
algal toxins, bacterial toxins, and
plant toxins
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 (1849–1 ...
(8). These marine biotoxins are dangerous to human health and have been widely studied due to their high potential to bioaccumulate in edible parts of seafood.
Autotrophic
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
and
algae
Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular mic ...
are unrelated organisms; however, in aquatic environments, they are both
primary producers
An autotroph or primary producer is an organism that produces complex organic compounds (such as carbohydrates, fats, and proteins) using carbon from simple substances such as carbon dioxide,Morris, J. et al. (2019). "Biology: How Life Works", ...
.
Cyanobacteria are an important autotrophic bacteria in the water food web. Explosions of
cyanobacteria
Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, blu ...
known as
algal bloom
An algal bloom or algae bloom is a rapid increase or accumulation in the population of algae in freshwater or marine water systems. It is often recognized by the discoloration in the water from the algae's pigments. The term ''algae'' encompas ...
s can produce toxins harmful to both the ecosystem and human health. These harmful
algal bloom
An algal bloom or algae bloom is a rapid increase or accumulation in the population of algae in freshwater or marine water systems. It is often recognized by the discoloration in the water from the algae's pigments. The term ''algae'' encompas ...
s are more likely to be produced at a dangerous amount when there is an excess of
nutrient
A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
s, the temperature is 20 °C, there is more light, and calmer waters.
Eutrophication
Eutrophication is the process by which an entire body of water, or parts of it, becomes progressively enriched with minerals and nutrients, particularly nitrogen and phosphorus. It has also been defined as "nutrient-induced increase in phytopla ...
and other contamination can lead to an environment that promotes
cyanobacteria blooms.
Processes that promote an excess of nutrients, and human activities, such as
agricultural runoff
Agricultural pollution refers to biotic and abiotic byproducts of farming practices that result in contamination or degradation of the environment and surrounding ecosystems, and/or cause injury to humans and their economic interests. The pol ...
and
sewage overflows, are primarily responsible.
Other factors include algal species and
grazers being in higher concentrations, allowing for an abundance of
cyanobacteria
Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, blu ...
l organisms that are associated with the production of
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– ...
s.
Detection of the extent of an algal bloom begins by taking samples of water at various depths and locations in the bloom.
Solid-phase adsorption toxin tracking (SPATT)
SPATT was introduced in 2004 as a method of monitoring aquatic
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– ...
s. This tool is able to adsorb toxins generated by
microalgae
Microalgae or microphytes are microscopic algae invisible to the naked eye. They are phytoplankton typically found in freshwater and marine systems, living in both the water column and sediment. They are unicellular species which exist indiv ...
or
cyanobacteria
Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, blu ...
, known as
cyanotoxin
Cyanotoxins are toxins produced by cyanobacteria (also known as blue-green algae). Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they exponential gr ...
s.
The adsorption is passive, and the
biotoxin
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– ...
s adhere to porous, resin filled sachets, or SPATT bags where they are then physically removed and examined.
SPATT is a useful tool in tracking algal blooms as it is reliable, sensitive, and inexpensive. It has the ability to quickly alert the existence of aquatic toxins which prevents it from bioaccumulating in marine life.
One of the downsides is that it does not give very good results for water-soluble toxins as compared to hydrophobic compounds. This tool is mainly used to determine intercellular concentrations of toxins but the cyanobacteria can also be lysed to determine the total toxin amount in a sample.
Other drawbacks, such as a lack in calibration and the ability to only monitor dissolved toxins, make it difficult for this tool to be implemented in a more widespread manner.
However,
SPATT devices are able to detect many
lipophilic
Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipop ...
and hydrophilic
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– ...
s that are linked to harmful
algal bloom
An algal bloom or algae bloom is a rapid increase or accumulation in the population of algae in freshwater or marine water systems. It is often recognized by the discoloration in the water from the algae's pigments. The term ''algae'' encompas ...
.
Polymerase chain reaction (PCR)
PCR is a molecular tool that allows for analysis of genetic information. PCR is used to amplify the amount of certain DNA within a sample which are usually specific genes within a sample. Genetic targets for cyanobacteria in PCR include the 16S ribosomal RNA gene, phycocyanin operon, internal transcribed spacer region, and the RNA polymerase β subunit gene. PCR is effective when the gene of a known enzyme for producing the microbial toxin or the microbial toxin itself is known.
One type of PCR is real time PCR also called quantitative PCR.
This type of PCR uses fluorescence and then does an analysis by measuring the amount of fluorescence that reflects the DNA sample more specifically nucleic acids at specific times.
Another type of PCR is digital PCR that looks at nucleic acid quantifications. Digital PCR uses dilutions and samples from microlitre reactions to achieve a more accurate quantification of nucleic acids. This type offers a more linear analysis by looking at the positive and negative reactions. Both PCR's are beneficial but there are advantages and disadvantages for both. The digital PCR has several advantages over real time PCR which includes no standard curve, more precise, less affected by simple inhibitors.
Digital also has disadvantages to real time which is limited reaction mixture time, more complex and high risk of contamination.
Enzyme inhibition
There are many diverse ways of monitoring enzyme levels through the use of enzyme inhibition. The general principle in many of these is the use the knowledge that many enzymes are driven by phosphate-releasing compounds such as
adenosine triphosphate
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...
. Using radiolabelled
32P phosphate a fluorometric analysis can be used. Or unique polymers can be used to immobilize enzymes and act in an electrochemical biosensor. Overall, the benefits include a fast response time and little sample preparation. Some of the downsides include a lack of specificity in terms of being able to get readings of very small amounts of toxin and the rigidity of the assays in apply certain procedures to different toxins.
Immunochemical methods
This detection method uses mammalian antibodies to bind to microbial toxins which can then be processed in a variety of different ways. Of the commercial ways of using immunochemical detection would be
enzyme-linked immunosorbent assays
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...
(ELISA). This assay has the advantage of being able to screen for a broad range of toxins but could have issues with specificity depending on the antibody used.
A more exotic setup involves the use of CdS
quantum dot
Quantum dots (QDs) are semiconductor particles a few nanometres in size, having light, optical and electronics, electronic properties that differ from those of larger particles as a result of quantum mechanics. They are a central topic in nanote ...
s which are used in an electro-chemiluminescent immunosensor. A major aspect of immunochemical methods being tested in laboratories are uses of
nanowire
A nanowire is a nanostructure in the form of a wire with the diameter of the order of a nanometre (10−9 metres). More generally, nanowires can be defined as structures that have a thickness or diameter constrained to tens of nanometers or less ...
s and other nanomaterials to detect microbial toxins.
Tetrodotoxins
These toxins are produced by
vibrio
''Vibrio'' is a genus of Gram-negative bacteria, possessing a curved-rod (comma) shape, several species of which can cause foodborne infection, usually associated with eating undercooked seafood. Being highly salt tolerant and unable to survive ...
species of bacteria and like to accumulate in marine life such as the pufferfish. These toxins are produced when vibrio bacteria are stressed by changes in temperature and salinity of environment which leads towards production of toxins. The main hazard towards humans is during consumption of contaminated seafood.
Tetrodotoxin
Tetrodotoxin (TTX) is a potent neurotoxin. Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish; several of these species carry the toxin. Although tetrodotoxin was discovered ...
poisoning is becoming common in more northern and typically colder marine waters as higher precipitation and warmer waters from climate change triggers vibrio bacteria to produce toxins.
Most of the marine life that produce this toxin are typically found in warm water for example the Red Sea and the Mediterranean Sea. For example, pufferfish do produce this toxin, some pufferfish, such as Takifugu V., produce tetrodotoxin in their skin glands. Another organism that releases the tetrodotoxin from their skin are blue-ringed octopuses (Hapalochlaena fasciata). The Natica Lineata snails produce the tetrodotoxin and store it in the muscle. The snail releases the toxin by absorbing water into the muscle cavity and it is released when the snail is attacked. Once a human consumes the toxin, the individual could experience mild symptoms such as paresthesias of the lips or tongue, vomiting and headaches. The individual could also experience severe symptoms such as respiratory or heart failure. At this time there is no treatment for tetrodotoxin poisoning other than respiratory support.
Viral toxin
Rotavirus NSP4
There is only one viral toxin that has been described so far:
NSP4 from
rotavirus
''Rotavirus'' is a genus of double-stranded RNA viruses in the family ''Reoviridae''. Rotaviruses are the most common cause of diarrhoeal disease among infants and young children. Nearly every child in the world is infected with a rotavirus a ...
. It inhibits the
microtubule
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
-mediated secretory pathway and alters
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
organization in polarized
epithelial cell
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
s. It has been identified as the viral
enterotoxin
An enterotoxin is a protein exotoxin released by a microorganism that targets the intestines.
Enterotoxins are chromosomally encoded or plasmid encoded exotoxins that are produced and secreted from several bacterial organisms. They are heat labi ...
based on the observation that the protein caused diarrhea when administered intraperitoneally or intra-ileally in infant mice in an age-dependent manner. NSP4 can induce aqueous secretion in the gastrointestinal tract of neonatal mice through activation of an age- and Ca2+-dependent plasma membrane anion permeability.
Virus involvement in toxigenicity
Several
bacteriophage
A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...
s contain toxin genes that become incorporated into the host bacteria genome through infection and render the bacteria toxic.
Many well known bacterial toxins are produced from specific strains of the bacteria species that have obtained toxigenicity through
lysogenic
Lysogeny, or the lysogenic cycle, is one of two cycles of viral reproduction (the lytic cycle being the other). Lysogeny is characterized by integration of the bacteriophage nucleic acid into the host bacterium's genome or formation of a circul ...
conversion, pseudolysogeny, or
horizontal gene transfer
Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between Unicellular organism, unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offsprin ...
.
Although these are not viral toxins, researchers remain extremely interested in the role phages play bacterial toxins due to their contribution to pathogenesis (toxigenesis), virulence, transmissibility and general evolution of bacteria.
Examples of toxins encoded by phage genes:
* Cholera toxins: encoded by CTX phages, virulent ''Vibrio cholerae'' strains require lysogenic conversion by CTX phage infection
* Several botulinum toxins (BoNTs): Type C and D BoNTS have been shown to be encoded by clostridial phages and are produced by ''Clostridium botulinum'' strains harboring these phage genes
* Shiga toxins: encoded by lambdoid phages, mainly produced by lysogenic shiga-toxin producing strains of ''E. coli'' (STEC)
* Diphtheria toxins: encoded by corynephage ß, produced by lysogenic ''Corynebacterium diphtheriae'' strains infected with corynephage ß
* Several staphylococci toxins (staphylokinase (SAK), staphylococcal enterotoxin A (SEA), exfoliative toxin (ETA), Panton-Valentine leucocidin (PVL), and other enterotoxins): toxins that are phage-encoded and produced by lysogenic converted strains of the staphylococci group.
Mycoviruses
Some mycoviruses also contain toxin genes expressed by host fungal species upon viral infection.
While these toxins are classified as mycotoxins, the role of mycoviruses is also of interest to researchers in terms of fungal virulence.
Examples include the mycoviruses ScV-M1, ScV-M2, and ScV-M28 in the
Totiviridae
''Totiviridae'' is a family of double-stranded RNA viruses. Giardia lamblia, leishmania, trichomonas vaginalis, and fungi serve as natural hosts. The name of the group derives from Latin ''toti'' which means undivided or whole. There are 28 spec ...
family that contain “
killer toxin” genes K1, K2, and K3, respectively.
These “killer toxins” are produced by yeast, namely of the ''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'' species, that destroy neighboring yeast cells.
Recently, researchers discovered that it is only the yeasts infected with either ScV-M1, ScV-M2, or ScV-M28 mycoviruses that have the ability to produce a “killer toxin.”
Mycotoxins
Mycotoxins are secondary metabolites that are constructed by microfungi.
Mycotoxins can be harmful because they can cause disease and death in humans and animals.
They are found in many pharmaceuticals like antibiotics and growth developments.
Mycotoxins can also play a role in chemical warfare agents, CWA, which are chemicals that contain toxins that are used to cause death, harm, or injuries to individuals that are considered enemies by the military during warfare.
Mycotoxins are synthesized by different types of moulds and are built by a wide group of toxins.
Mycotoxins have a low molecular weight compound that is usually less than 1000 grams per mol.
There are roughly 400 toxic mycotoxins that are constructed by 100 different fungi species that have been researched.
Mycotoxins gain access into the body of a human or animal by food, they can contaminate many different types of agriculture during cultivation, harvesting, storage, and areas with high humidity.
The Food and Agriculture Organization reported that about 25% of products produced by agriculture contain mycotoxins and this can lead to economic losses in the agricultural community.
Levels of Mycotoxins secretion can rely on varying temperatures, the ideal temperature for Mycotoxins to grow is from 20 degrees Celsius to 37 degrees Celsius.
Mycotoxin production also relies heavily on water activity, the ideal range would be from 0.83 to 0.9 aw and higher.
Humidity plays a key in the production of Mycotoxins as well.
The higher the humidity levels, between 70% to 90%, and moisture levels, 20% to 25%, allow the Mycotoxins to grow more rapidly.
Foods that Mycotoxins are found in cereal, spices, and seeds.
They can also be found in eggs, milk, and meat from animals that have been contaminated during their feeding process.
Since they are resistant to high temperatures and physical and chemical reception, it is considered unavoidable while cooking at high temperatures.
Types
Trichothecenes is a mycotoxin that is produced from the fungi species, Fusarium graminearum.
The T-2 toxin, Type A, and DON, Type B, are major mycotoxins that are responsible for toxicity in humans and animals.
These two types come from an epoxide at the C12 and C13 positions in the trichothecenes.
The T-2 toxin was found after civilians ate wheat that was contaminated by the Fusarium Fungi, during WWII from a biological weapon, the T-2 toxin was an outbreak and made humans develop symptoms like food poisoning, chills, nausea, dizziness, etc.
The Trichothecenes mycotoxin affects animals by decreasing plasma glucose, blood cell and leukocyte counts.
Pathological changes in the liver and stomach, as well as weight loss has been accounted for.
Zearalenone is a mycotoxin that is produced from Fusarium graminearum and Fusarium culmorum that are found in different types of foods and feeds.
Zearalenone is a non-steroidal estrogenic mycotoxin that is found in farm animal's reproductive disorders and in humans it causes hypoestrogenic syndrome.
Effects that come from Zearalenone include, enlarged uterus, improperly running reproductive tract, decreasing the fertility in women, and causes progesterone and estradiol levels to become not normal.
If Zearalenone is consumed during pregnancy, it can cause reduced fetal weight and decrease the chance of survival for the embryo.
Fumonisins, Fusarium verticillioides, is found in nature where fumonisin B1 has largely contaminated the area.
These mycotoxins are hydrophilic compounds. Studies have shown that esophageal cancer can be related back to corn grain that contains fumonisins.
Other effects from fumonisins are birth defects of the brain, spine, and spinal cord.
In animals, problems with the pulmonary edema and hydrothorax swine's have been proven to have association with fumonisins.
Ochratoxin is a mycotoxin that is produced by Aspergillus species and Penicillium species.
The most researched ochratoxin is the Ochratoxin A (OTA), which is a fungal toxin.
This mycotoxin targets the OTA of kidneys and causes kidney disease in humans.
Ochratoxin A is an immunosuppressive compound.
Ochratoxin is a renal carcinogen, which has been found by animals containing OTA.
Aflatoxin is a mycotoxin that is produced from Aspergillus flavus and Aspergillus parasititcus.
A type of Aflatoxin, AFB1 is the most common mycotoxin that is found in human food and animal feed.
AFB1 targets the liver of both humans and animals.
Acute aflatoxicosis can make humans and animals have symptoms like abdominal pain, vomiting, and even death.
See also
*
Alpha 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 ...
*
Dinotoxin Dinotoxins are a group of toxins which are produced by flagellate, aquatic, unicellular protists called dinoflagellates. Dinotoxin was coined by Hardy and Wallace in 2012 as a general term for the variety of toxins produced by dinoflagellates. Dinof ...
*
Cyanotoxin
Cyanotoxins are toxins produced by cyanobacteria (also known as blue-green algae). Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they exponential gr ...
*
Diphtheria toxin
Diphtheria toxin is an exotoxin secreted by '' Corynebacterium diphtheriae'', the pathogenic bacterium that causes diphtheria. The toxin gene is encoded by a prophageA prophage is a virus that has inserted itself into the genome of the host ...
*
Exotoxin
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, simi ...
*
Pertussis toxin
Pertussis toxin (PT) 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. Res ...
*
Shiga toxin
Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial orig ...
*
Shiga-like toxin
Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial or ...
References
External links
*{{Commons category-inline, Microbial toxins
Microbiology
Toxins by type of organism