Exotoxins
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An exotoxin is a
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– ...
secreted by
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 ...
. An exotoxin can cause damage to the host by destroying cells or disrupting normal
cellular metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...
. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to
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, may be released during
lysis Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
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 Membrane vesicle trafficking in eukaryotic animal cells involves movement of biochemical signal molecules from synthesis-and-packaging locations in the Golgi body to specific release locations on the inside of the plasma membrane of the secretory ...
, 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 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 ...
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 ...
''; ''
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 ...
'' toxin, produced during life-threatening symptoms of
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 ...
;
tetanospasmin Tetanus toxin (TeNT) is an extremely potent neurotoxin produced by the vegetative cell of ''Clostridium tetani'' in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally ...
produced by ''
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 ...
''. The toxic properties of most exotoxins can be inactivated by heat or chemical treatment to produce a
toxoid A toxoid is an inactivated toxin (usually an exotoxin) whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, wherea ...
. These retain their antigenic specificity and can be used to produce
antitoxin An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacterium, bacteria in response to toxin exposure. Although they are most effective in neutralizing toxins, the ...
s and, in the case of diphtheria and tetanus toxoids, are used as vaccines. Exotoxins are susceptible to
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
produced 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 ...
, but some exotoxins are so toxic that they may be fatal to the host before the immune system has a chance to mount defenses against them. In such cases, antitoxin, anti-serum containing antibodies, can sometimes be injected to provide
passive immunity Passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when hi ...
.


Types

Many exotoxins have been categorized. This classification, while fairly exhaustive, is not the only system used. Other systems for classifying or identifying toxins include: * By organism generating the toxin * By organism susceptible to the toxin * By secretion system used to release the toxin (for example, toxic effectors of type VI secretion system) * By tissue target type susceptible to the toxin (
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 ...
s affect the nervous system,
cardiotoxin Cardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity. The heart becomes weaker and is not as efficient in pumping blood. Cardiotoxicity may be caused by chemotherapy (a usual example is th ...
s affect the heart, etc.) * By structure (for example,
AB5 toxin The AB5 toxins are six-component protein complexes secreted by certain pathogenic bacteria known to cause human diseases such as cholera, dysentery, and hemolytic–uremic syndrome. One component is known as the A subunit, and the remaining fi ...
) * By domain architecture of the toxin (for example,
polymorphic toxins Polymorphic toxins (PTs) are multi-domain proteins primarily involved in competition between bacteria but also involved in pathogenesis when injected in eukaryotic cells. They are found in all major bacterial clades. Bacteria live in complex multi ...
) * By the ability of the toxin to endure in hostile environments, such as heat, dryness, radiation, or salinity. In this context, "labile" implies susceptibility, and "stable" implies a lack of susceptibility. * By a letter, such as "A", "B", or "C", to communicate the order in which they were identified. The same exotoxin may have different names, depending on the field of research.


Type I: cell surface-active

Type I toxins bind to a receptor on the cell surface and stimulate intracellular signaling pathways. Two examples are described below.


Superantigens

Superantigens 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 ...
are produced by several bacteria. The best-characterized superantigens are those produced by the strains of ''
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 ...
'' and ''
Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus ''Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They are ...
'' that cause
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 ...
. Superantigens bridge the
MHC class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, ...
protein on
antigen-presenting cells An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...
with the
T-cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...
on the surface of
T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...
with a particular Vβ chain. As a consequence, up to 50% of all T cells are activated, leading to massive secretion of proinflammatory
cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
, which produce the symptoms of toxic shock.


Heat-stable enterotoxins

Some strains of ''
E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'' produce
heat-stable enterotoxin Heat-stable enterotoxins (STs) are secretory peptides produced by some bacterial strains, such as enterotoxigenic ''Escherichia coli'' which are in general toxic to animals. These peptides keep their 3D structure and remain active at temperatu ...
s (ST), which are small peptides that are able to withstand heat treatment at 100 °C. Different STs recognize distinct receptors on the cell surface and thereby affect different intracellular signaling pathways. For example, STa enterotoxins bind and activate membrane-bound guanylate cyclase, which leads to the intracellular accumulation of
cyclic GMP Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in re ...
and downstream effects on several signaling pathways. These events lead to the loss of electrolytes and water from intestinal cells.


Type II: membrane damaging

Membrane-damaging toxins exhibit
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 ...
or cytolysin activity ''in vitro''. However, induction of cell lysis may not be the primary function of the toxins during infection. At low concentrations of toxin, more subtle effects such as modulation of host cell signal transduction may be observed in the absence of cell lysis. Membrane-damaging toxins can be divided into two categories, the channel-forming toxins and toxins that function as enzymes that act on the membrane.


Channel-forming toxins

Most channel-forming toxins, which form pores in the target cell membrane, can be classified into two families: the cholesterol-dependent toxins and the RTX toxins. * Cholesterol-dependent cytolysins Formation of pores by
cholesterol-dependent cytolysin The thiol-activated Cholesterol-dependent Cytolysin (CDC) familyTC# 1.C.12 is a member of the MACPF superfamily. Cholesterol dependent cytolysins are a family of β-barrel pore-forming exotoxins that are secreted by gram-positive bacteria. CDCs ...
s (CDC) requires the presence of
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
in the target cell. The size of the pores formed by members of this family is extremely large: 25-30 nm in diameter. All CDCs are secreted by the type II
secretion 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
system; the exception is
pneumolysin Pneumolysin is a virulence factor of the Gram-positive bacteria ''Streptococcus pneumoniae''. It is a pore-forming toxin of 53 kDa composed of 471 amino acids. It has a range of biological activity, including the ability to lyse and interfere wi ...
, which is released from the cytoplasm of ''
Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They are ...
'' when the bacteria lyse. The CDCs ''Streptococcus pneumoniae'' Pneumolysin, ''
Clostridium perfringens ''Clostridium perfringens'' (formerly known as ''C. welchii'', or ''Bacillus welchii'') is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus '' Clostridium''. ''C. perfringens'' is ever-present in nature an ...
'' perfringolysin O, and ''
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' ...
''
listeriolysin O Listeriolysin O (LLO) is a hemolysin produced by the bacterium ''Listeria monocytogenes'', the pathogen responsible for causing listeriosis. The toxin may be considered a virulence factor, since it is crucial for the virulence of ''L. monocytogenes ...
cause specific modifications of
histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...
s in the host
cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...
, resulting in down-regulation of several genes that encode proteins involved in the
inflammatory response Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...
. Histone modification does not involve the pore-forming activity of the CDCs. * RTX toxins
RTX toxin The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein se ...
s can be identified by the presence of a specific tandemly repeated nine-amino acid residue sequence in the protein. The prototype member of the RTX toxin family is
haemolysin A 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 acq ...
(HlyA) of ''E. coli''. RTX is also found in ''
Legionella pneumophila ''Legionella pneumophila'' is a thin, aerobic, pleomorphic, flagellated, non-spore-forming, Gram-negative bacterium of the genus ''Legionella''. ''L. pneumophila'' is the primary human pathogenic bacterium in this group and is the causative age ...
''.


Enzymatically active toxins

One example is the α toxin of ''C. perfringens'', which causes
gas gangrene Gas gangrene (also known as clostridial myonecrosis and myonecrosis) is a bacterial infection that produces tissue gas in gangrene. This deadly form of gangrene usually is caused by ''Clostridium perfringens'' bacteria. About 1,000 cases of gas g ...
; α toxin has
phospholipase A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. Acids trigger the release of bound calcium from cellular stores and the consequent increase in free cytosolic Ca2+, an essential step in ...
activity.


Type III: intracellular

Type III exotoxins can be classified by their mode of entry into the cell, or by their mechanism once inside.


By mode of entry

Intracellular toxins must be able to gain access to the cytoplasm of the target cell to exert their effects. * Some bacteria deliver toxins directly from their cytoplasm to the cytoplasm of the target cell through a needle-like structure. The effector proteins injected by the type III
secretion 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
apparatus of ''
Yersinia ''Yersinia'' is a genus of bacteria in the family Yersiniaceae. ''Yersinia'' species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of ''Ye ...
'' into target cells are one example. * Another group of intracellular toxins is the
AB toxin The AB toxins are two-component protein complexes secreted by a number of pathogenicity, pathogenic bacteria, though there is a pore-forming AB toxin found the eggs of a snail. They can be classified as Exotoxin#Type III: intracellular, Type III t ...
s. The 'B'-subunit (''binding'') attaches to target regions on cell membranes, the 'A'-subunit (''active'') enters through the membrane and possesses
enzymatic Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
function that affects internal cellular bio-mechanisms. A common example of this A-subunit activity is called
ADP-ribosylation ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. It is a reversible post-translational modification that is involved in many cellular processes, including cell signaling, DNA repair, gene regulation and apoptosis. ...
in which the A-subunit catalyzes the addition of an ADP-ribose group onto specific residues on a protein. The structure of these toxins allows for the development of specific
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
s and treatments. Certain compounds can be attached to the B unit, which is not, in general, harmful, which the body learns to recognize, and which elicits an
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
. This allows the body to detect the harmful toxin if it is encountered later, and to eliminate it before it can cause harm to the host. Toxins of this type include
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 ...
,
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 ...
and heat-labile
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 ...
from ''E. coli''.


By mechanism

Once in the cell, many of the exotoxins act at the eukaryotic
ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
s (especially 60S), as
protein synthesis inhibitor A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. While a broad interpretation of this definition could be used t ...
s. (Ribosome structure is one of the most important differences between eukaryotes and prokaryotes, and, in a sense, these exotoxins are the bacterial equivalent of antibiotics such as
clindamycin Clindamycin is an antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media (middle ear infec ...
.) * Some exotoxins act directly at the ribosome to inhibit protein synthesis. An example is
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 ...
. * Other toxins act at
elongation factor-2 Eukaryotic elongation factor 2 is a protein that in humans is encoded by the ''EEF2'' gene. It is the archaeal and eukaryotic counterpart of bacterial EF-G. This gene encodes a member of the Guanosine triphosphate, GTP-binding translation elongat ...
. In the case of the
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 ...
, EF2 is ADP-ribosylated and becomes unable to participate in protein elongation, and, so, the cell dies.
Pseudomonas exotoxin The Pseudomonas exotoxin (or exotoxin A) is an exotoxin produced by ''Pseudomonas aeruginosa''. ''Vibrio cholerae'' produces a similar protein called the Cholix toxin (). It inhibits elongation factor-2. It does so by ADP-ribosylation of EF ...
has a similar action. Other intracellular toxins do not directly inhibit protein synthesis. * For example,
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 ...
ADP-ribosylates, thereby activating tissue adenylate cyclase to increase the concentration of cAMP, which causes the movement of massive amounts of fluid and electrolytes from the lining of the small intestine and results in life-threatening diarrhea. * Another example is
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 ...
.


Extracellular matrix damage

These "toxins" allow the further spread of bacteria and, as a consequence, deeper tissue infections. Examples are
hyaluronidase Hyaluronidases are a family of enzymes that catalyse the degradation of hyaluronic acid (HA). Karl Meyer classified these enzymes in 1971, into three distinct groups, a scheme based on the enzyme reaction products. The three main types of hyal ...
and
collagenase Collagenases are enzymes that break the peptide bonds in collagen. They assist in destroying extracellular structures in the pathogenesis of bacteria such as ''Clostridium''. They are considered a virulence factor, facilitating the spread of ...
. These molecules, however, are enzymes that are secreted by a variety of organisms and are not usually considered toxins. They are often referred to as
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 ...
s, since they allow the organisms to move deeper into the hosts tissues.


Medical applications


Vaccinations

Exotoxins have been used to produce vaccines. This process involves inactivating the toxin, creating a
toxoid A toxoid is an inactivated toxin (usually an exotoxin) whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, wherea ...
that does not induce toxin-related illness and is well tolerated. A widely used toxoid vaccine is the
DPT vaccine The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus. The vaccine components include diphtheria and tetanus toxoids and either kille ...
, which is usually administered in multiple doses throughout childhood with
adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Analgesic ...
s and boosters for long-term immunity. DPT vaccine protects against
pertussis Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by two or ...
,
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 ...
and
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 ...
infections, caused by the exotoxin-producing ''
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 ...
'', ''
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 ...
'' and ''
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 ...
'' respectively. Vaccination with the toxoids generates antibodies against the exotoxins, forming immunological memory as protection against subsequent infections. The DPT vaccination may cause adverse side effects, such as swelling, redness and fever, and is contraindicated in some populations. Effective vaccination schedules have reduced rates of mortality linked to pertussis, tetanus and diphtheria but formal controlled trials to test the efficacy of the vaccine have not been conducted. Additionally, pertussis persists endemically and is one of the most common causes of vaccine-preventable deaths.


Cancer treatment

As exotoxins are highly potent, there has been development in their application to cancer treatment. Cancer cells can be eliminated without destroying normal cells like in chemotherapy or radiation by attaching an antibody or receptor ligand to the exotoxin, creating a recombinant toxin that is targeted to certain cells. The cancer cell is killed once the toxin is internalized; for example,
Pseudomonas exotoxin The Pseudomonas exotoxin (or exotoxin A) is an exotoxin produced by ''Pseudomonas aeruginosa''. ''Vibrio cholerae'' produces a similar protein called the Cholix toxin (). It inhibits elongation factor-2. It does so by ADP-ribosylation of EF ...
disrupts protein synthesis after cellular uptake. Multiple versions of recombinant exotoxin A, secreted by ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerugi ...
'', have entered clinical trials against tumor growth but have yet to be approved by
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA). A recombinant diphtheria exotoxin has been approved by the FDA for treatment of
cutaneous T-cell lymphoma Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, which is a type of cancer of the immune system. Unlike most non-Hodgkin lymphomas (which are generally B-cell-related), CTCL is caused by a mutation of T cells. The cancerous ...
, an immune system cancer. Further testing to improve clinical efficacy of treatment using recombinant exotoxins continues.


See also

*
Infectious disease An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
*
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' ...
*
Membrane vesicle trafficking Membrane vesicle trafficking in eukaryotic animal cells involves movement of biochemical signal molecules from synthesis-and-packaging locations in the Golgi body to specific release locations on the inside of the plasma membrane of the secretory ...


References


External links

* * {{Toxins Toxins Microbiology