
A toxin-antitoxin system consists of a "toxin" and a corresponding "antitoxin", usually encoded by closely linked genes. The toxin is usually a protein while the antitoxin can be a protein or an RNA. Toxin-antitoxin systems are widely distributed in
prokaryote
A prokaryote (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...
s, and organisms often have them in multiple copies.
When these systems are contained on
plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria and ...
s – transferable genetic elements – they ensure that only the daughter cells that
inherit the plasmid survive after
cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
. If the plasmid is absent in a daughter cell, the unstable
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 ...
is degraded and the stable toxic protein kills the new cell; this is known as 'post-segregational killing'
(PSK).
Toxin-antitoxin systems are typically classified according to how the antitoxin neutralises the toxin. In a type I toxin-antitoxin system, the
translation
Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...
of
messenger RNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
(mRNA) that encodes the toxin is inhibited by the binding of a small
non-coding RNA
A non-coding RNA (ncRNA) is a functional RNA molecule that is not Translation (genetics), translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally imp ...
antitoxin that binds the toxin mRNA. The toxic protein in a type II system is inhibited post-translationally by the binding of an antitoxin
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
. Type III toxin-antitoxin systems consist of a small RNA that binds directly to the toxin protein and inhibits its activity.
There are also types IV, V and VI, which are less common. Toxin-antitoxin
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
s are often inherited through
horizontal gene transfer
Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the e ...
and are associated with
pathogenic bacteria
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 many are Probiotic, beneficial but others can cause infectious diseases. The nu ...
, having been found on plasmids conferring
antibiotic resistance
Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resis ...
and
virulence
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most cases, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its abili ...
.
Chromosomal
A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most importa ...
toxin-antitoxin systems also exist, some of which are thought to perform cell functions such as responding to
stresses, causing
cell cycle
The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...
arrest and bringing about
programmed cell death
Programmed cell death (PCD) sometimes referred to as cell, or cellular suicide is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usual ...
.
In
evolution
Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...
ary terms, toxin-antitoxin systems can be considered
selfish DNA
Selfish genetic elements (historically also referred to as selfish genes, ultra-selfish genes, selfish DNA, parasitic DNA and genomic outlaws) are genetic segments that can enhance their own transmission at the expense of other genes in the genome, ...
in that the purpose of the systems are to replicate, regardless of whether they benefit the host organism or not. Some have proposed adaptive theories to explain the evolution of toxin-antitoxin systems; for example, chromosomal toxin-antitoxin systems could have evolved to prevent the inheritance of large
deletions of the host genome.
Toxin-antitoxin systems have several
biotechnological applications, such as maintaining plasmids in
cell lines
An immortalised cell line is a population of cells from a multicellular organism that would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...
, targets for
antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s, and as positive selection vectors.
Biological functions
Stabilization and fitness of mobile DNA
As stated above, toxin-antitoxin systems are well characterized as plasmid addiction modules. It was also proposed that toxin-antitoxin systems have
evolved
Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...
as plasmid exclusion modules. A cell that carries two plasmids from the same
incompatibility group will eventually generate two daughter cells carrying either plasmid. Should one of these plasmids encode for a TA system, its "displacement" by another TA-free plasmid system will prevent its inheritance and thus induce post-segregational killing. This theory was corroborated through
computer modelling
Computer simulation is the running of a mathematical model on a computer, the model being designed to represent the behaviour of, or the outcome of, a real-world or physical system. The reliability of some mathematical models can be determin ...
.
Toxin-antitoxin systems can also be found on other
mobile genetic elements
Mobile genetic elements (MGEs), sometimes called selfish genetic elements, are a type of genetic material that can move around within a genome, or that can be transferred from one species or replicon to another. MGEs are found in all organisms. In ...
such as conjugative
transposons
A transposable element (TE), also transposon, or jumping gene, is a type of mobile genetic element, a nucleic acid sequence in DNA that can change its position within a genome.
The discovery of mobile genetic elements earned Barbara McClinto ...
and
temperate
In geography, the temperate climates of Earth occur in the middle latitudes (approximately 23.5° to 66.5° N/S of the Equator), which span between the tropics and the polar regions of Earth. These zones generally have wider temperature ran ...
bacteriophage
A bacteriophage (), also known informally as a phage (), is a virus that infects and replicates within bacteria. The term is derived . Bacteriophages are composed of proteins that Capsid, encapsulate a DNA or RNA genome, and may have structu ...
s and could be implicated in the maintenance and competition of these elements.
Genome stabilization

Toxin-antitoxin systems could prevent harmful large
deletions in a bacterial
genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
, though arguably deletions of large coding regions are fatal to a daughter cell regardless.
In ''Vibrio cholerae'', multiple type II toxin-antitoxin systems located in a
super-integron were shown to prevent the loss of gene cassettes.
Altruistic cell death
''mazEF'', a toxin-antitoxin locus found in ''E. coli'' and other bacteria, was proposed to induce programmed cell death in response to
starvation
Starvation is a severe deficiency in caloric energy intake, below the level needed to maintain an organism's life. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, de ...
, specifically a lack of
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s. This would release the cell's contents for absorption by neighbouring cells, potentially preventing the death of close relatives, and thereby increasing the
inclusive fitness
Inclusive fitness is a conceptual framework in evolutionary biology first defined by W. D. Hamilton in 1964. It is primarily used to aid the understanding of how social traits are expected to evolve in structured populations. It involves partit ...
of the cell that perished. This would be an example of
altruism
Altruism is the concern for the well-being of others, independently of personal benefit or reciprocity.
The word ''altruism'' was popularised (and possibly coined) by the French philosopher Auguste Comte in French, as , for an antonym of egoi ...
and how
bacterial colonies could resemble
multicellular organism
A multicellular organism is an organism that consists of more than one cell (biology), cell, unlike unicellular organisms. All species of animals, Embryophyte, land plants and most fungi are multicellular, as are many algae, whereas a few organism ...
s.
However, the "''mazEF''-mediated PCD" has largely been refuted by several studies.
Stress tolerance
Another theory states that chromosomal toxin-antitoxin systems are designed to be
bacteriostatic
A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfec ...
rather than
bactericidal
A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria. Bactericides are disinfectants, antiseptics, or antibiotics.
However, material surfaces can also have bactericidal properties based solely on their p ...
.
RelE, for example, is a global inhibitor of translation, is induced during
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 ...
stress. By shutting down translation under stress, it could reduce the chance of starvation by lowering the cell's nutrient requirements.
However, it was shown that several toxin-antitoxin systems, including ''relBE'', do not give any competitive advantage under any stress condition.
Anti-addiction
It has been proposed that chromosomal homologues of plasmid toxin-antitoxin systems may serve as anti-
addiction module
Addiction modules are toxin-antitoxin systems. Each consists of a pair of genes that specify two components: a stable toxin and an unstable antitoxin that interferes with the lethal action of the toxin. Found first in ''Escherichia coli'' on low c ...
s, which would allow progeny to lose a plasmid without suffering the effects of the toxin it encodes.
For example, a chromosomal copy of ''the ccdA'' antitoxin encoded in the chromosome of ''
Erwinia chrysanthemi
''Dickeya dadantii'' is a Gram-negative Bacillus (shape), bacillus that belongs to the family Pectobacteriaceae. It was formerly known as ''Erwinia chrysanthemi'' but was reassigned as ''Dickeya dadantii'' in 2005. Members of this family are facu ...
'' is able to neutralize the ''ccdB'' toxin encoded on the
F plasmid and thus, prevent toxin activation when such a plasmid is lost. Similarly, the ''ataR'' antitoxin encoded on the chromosome of
''E. coli'' O157:H7 is able neutralize the ''ataT
P'' toxin encoded on plasmids found in other
enterohemorragic ''E. coli''.
Phage protection
Type III toxin-antitoxin (AbiQ) systems have been shown to protect bacteria from
bacteriophage
A bacteriophage (), also known informally as a phage (), is a virus that infects and replicates within bacteria. The term is derived . Bacteriophages are composed of proteins that Capsid, encapsulate a DNA or RNA genome, and may have structu ...
s altruistically.
During an infection, bacteriophages hijack transcription and translation, which could prevent antitoxin replenishment and release toxin, triggering what is called an "abortive infection".
Similar protective effects have been observed with type I,
type II,
and type IV (AbiE) toxin-antitoxin systems.
Abortive initiation (Abi) can also happen without toxin-antitoxin systems, and many Abi proteins of other types exist. This mechanism serves to halt the replication of phages, protecting the overall population from harm.
Antimicrobial persistence
When bacteria are challenged with antibiotics, a small and distinct subpopulation of cells is able to withstand the treatment by a phenomenon dubbed as "persistence" (not to be confused with
resistance).
Due to their bacteriostatic properties, type II toxin-antitoxin systems have previously been thought to be responsible for persistence, by switching a fraction of the bacterial population to a dormant state. However, this hypothesis has been widely invalidated.
Selfish DNA
Toxin-antitoxin systems have been used as examples of selfish DNA as part of the
gene centered view of evolution. It has been theorised that toxin-antitoxin loci serve only to maintain their own DNA, at the expense of the host organism.
Thus, chromosomal toxin-antitoxin systems would serve no purpose and could be treated as "junk DNA". For example, the ''ccdAB'' system encoded in the chromosome of
''E. coli'' O157:H7 has been shown to be under negative selection, albeit at a slow rate due to its addictive properties.
System types
Type I

Type I toxin-antitoxin systems rely on the
base-pairing
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
of complementary antitoxin
RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
with the toxin
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
. Translation of the mRNA is then inhibited either by degradation via
RNase III or by occluding the
Shine-Dalgarno sequence or
ribosome binding site
A ribosome binding site, or ribosomal binding site (RBS), is a sequence of nucleotides upstream of the start codon of an mRNA transcript that is responsible for the recruitment of a ribosome during the initiation of translation. Mostly, RBS refers ...
of the toxin mRNA. Often the toxin and antitoxin are encoded on opposite strands of DNA. The
5' or
3' overlapping region between the two genes is the area involved in
complementary base-pairing, usually with between 19–23 contiguous base pairs.
Toxins of type I systems are small,
hydrophobic
In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, thu ...
proteins that confer toxicity by damaging
cell membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
s.
Few intracellular targets of type I toxins have been identified, possibly due to the difficult nature of analysing proteins that are poisonous to their bacterial hosts.
Also, the detection of small proteins has been challenging due to technical issues, a problem that remains to be solved with large-scale analysis.
Type I systems sometimes include a third component. In the case of the well-characterised
''hok''/''sok'' system, in addition to the ''hok'' toxin and ''sok'' antitoxin, there is a third gene, called ''mok''. This
open reading frame
In molecular biology, reading frames are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible reading frames ...
almost entirely overlaps that of the toxin, and the translation of the toxin is dependent on the translation of this third component.
Thus the binding of antitoxin to toxin is sometimes a simplification, and the antitoxin in fact binds a third RNA, which then affects toxin
translation
Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...
.
Example systems
Type II

Type II toxin-antitoxin systems are generally better-understood than type I.
In this system a
labile
Lability refers to the degree that something is likely to undergo change. It is the opposite ( antonym) of stability.
Biochemistry
In reference to biochemistry, this is an important concept as far as kinetics is concerned in metalloprotein ...
proteic antitoxin tightly binds and inhibits the activity of a stable toxin.
The largest family of type II toxin-antitoxin systems is ''
vapBC'', which has been found through
bioinformatics
Bioinformatics () is an interdisciplinary field of science that develops methods and Bioinformatics software, software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, ...
searches to represent between 37 and 42% of all predicted type II loci.
Type II systems are organised in
operon
In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...
s with the antitoxin protein typically being located
upstream of the toxin, which helps to prevent expression of the toxin without the antitoxin. The proteins are typically around 100
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s in length,
and exhibit toxicity in a number of ways:
CcdB, for example, affects
DNA replication
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...
by poisoning
DNA gyrase
DNA gyrase, or simply gyrase, is an enzyme within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA-po ...
whereas toxins from the MazF family are endoribonucleases that cleave cellular mRNAs, tRNAs or rRNAs at specific
sequence motif
In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and usually assumed to be related to biological function of the macromolecule. For example, an ''N''-glycosylation site motif can be defined as ''A ...
s. The most common toxic activity is the protein acting as an
endonuclease
In molecular biology, endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain (namely DNA or RNA). Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (with regard to sequence), while man ...
, also known as an
interferase.
One of the key features of the TAs is the autoregulation. The antitoxin and toxin protein complex bind to the operator that is present upstream of the TA genes. This results in repression of the TA operon. The key to the regulation are (i) the differential translation of the TA proteins and (ii) differential proteolysis of the TA proteins. As explained by the "Translation-reponsive model", the degree of expression is inversely proportional to the concentration of the repressive TA complex. The TA complex concentration is directly proportional to the global translation rate. The higher the rate of translation more TA complex and less transcription of TA mRNA. Lower the rate of translation, lesser the TA complex and higher the expression. Hence, the transcriptional expression of TA operon is inversely proportional to translation rate.
A third protein can sometimes be involved in type II toxin-antitoxin systems. in the case of the ω-ε-ζ (omega-epsilon-zeta) system, the omega protein is a
DNA binding protein
DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, becau ...
that negatively regulates the transcription of the whole system.
Similarly, the ''paaR2'' protein regulates the expression of the ''paaR2-paaA2-parE2'' toxin-antitoxin system. Other toxin-antitoxin systems can be found with a
chaperone as a third component. This chaperone is essential for proper
folding of the antitoxin, thus making the antitoxin addicted to its cognate chaperone.
Example systems
Type III
Type III toxin-antitoxin systems rely on direct interaction between a toxic protein and an RNA antitoxin. The toxic effects of the protein are neutralised by the RNA gene.
One example is the ToxIN system from the bacterial plant pathogen ''
Erwinia carotovora
''Pectobacterium carotovorum'' is a bacterium of the family Pectobacteriaceae; it used to be a member of the genus ''Erwinia''.
The species is a plant pathogen with a diverse host range, including many agriculturally and scientifically impo ...
''. The toxic ToxN protein is approximately 170 amino acids long and has been shown to be toxic to ''
E. coli
''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...
''. The toxic activity of ToxN is inhibited by ToxI RNA, an RNA with 5.5 direct
repeats of a 36 nucleotide motif (AGGTGATTTGCTACCTTTAAGTGCAGCTAGAAATTC).
Crystallographic analysis of ToxIN has found that ToxN inhibition requires the formation of a trimeric ToxIN complex, whereby three ToxI monomers bind three ToxN monomers; the complex is held together by extensive protein-RNA interactions.
Type IV
Type IV toxin-antitoxin systems are similar to type II systems, because they consist of two proteins. Unlike type II systems, the antitoxin in type IV toxin-antitoxin systems counteracts the activity of the toxin, and the two proteins do not necessarily interact directly. DarTG1 and DarTG2 are type IV toxin-antitoxin systems that modify DNA. Their toxins add ADP-ribose to guanosine bases (DarT1 toxin) or thymidine bases (DarT2 toxin), and their antitoxins remove the toxic modifications (NADAR antitoxin from guanosine and DarG antitoxin from thymidine).
Type V
''ghoST'' is a type V toxin-antitoxin system, in which the antitoxin (GhoS) cleaves the ''ghoT'' mRNA. This system is regulated by a type II system, ''mqsRA''.
Type VI
''socAB'' is a type VI toxin-antitoxin system that was discovered in ''
Caulobacter crescentus''. The antitoxin, SocA, promotes degradation of the toxin, SocB, by the
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...
ClpXP.
Type VII
Type VII has been proposed to include systems ''hha/tomB'', ''tglT/takA'' and ''hepT/mntA'', all of which neutralise toxin activity by post-translational chemical modification of amino acid residues.
Type VIII
Type VIII includes the system ''creTA.'' In this system, the antitoxin ''creA'' serves as a guide RNA for a CRISPR-Cas system. Due to incomplete complementarity between the ''creA'' guide and the ''creAT'' promoter, the Cas complex does not cleave the DNA, but instead remains at the site, where it blocks access by RNA polymerase, preventing expression of the ''creT'' toxin (a natural instance of
CRISPRi). When expressed, the ''creT'' RNA will sequester the rare arginine codon tRNA
UCU, stalling translation and halting cell metabolism.
Biotechnological applications
The
biotechnological applications of toxin-antitoxin systems have begun to be realised by several biotechnology organisations.
A primary usage is in maintaining plasmids in a large bacterial
cell culture
Cell culture or tissue culture is the process by which cell (biology), cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been Cell isolation, isolated from living tissue, ...
. In an experiment examining the effectiveness of the ''hok''/''sok'' locus, it was found that segregational stability of an
inserted plasmid expressing
beta-galactosidase was increased by between 8 and 22 times compared to a
control culture lacking a toxin-antitoxin system.
In large-scale
microorganism
A microorganism, or microbe, is an organism of microscopic scale, microscopic size, which may exist in its unicellular organism, single-celled form or as a Colony (biology)#Microbial colonies, colony of cells. The possible existence of unseen ...
processes such as
fermentation
Fermentation is a type of anaerobic metabolism which harnesses the redox potential of the reactants to make adenosine triphosphate (ATP) and organic end products. Organic molecules, such as glucose or other sugars, are catabolized and reduce ...
, progeny cells lacking the plasmid insert often have a higher
fitness than those who inherit the plasmid and can outcompete the desirable microorganisms. A toxin-antitoxin system maintains the plasmid thereby maintaining the efficiency of the industrial process.
Additionally, toxin-antitoxin systems may be a future target for
antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s. Inducing suicide modules against pathogens could help combat the growing problem of
multi-drug resistance.
Ensuring a plasmid accepts an insert is a common problem of DNA
cloning
Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without ...
. Toxin-antitoxin systems can be used to positively select for only those cells that have taken up a plasmid containing the inserted gene of interest, screening out those that lack the inserted gene. An example of this application comes from the ''ccdB''-encoded toxin, which has been incorporated into
plasmid vectors.
The gene of interest is then targeted to recombine into the ''ccdB'' locus, inactivating the transcription of the toxic protein. Thus, cells containing the plasmid but not the insert perish due to the toxic effects of CcdB protein, and only those that incorporate the insert survive.
Another example application involves both the CcdB toxin and CcdA antitoxin. CcdB is found in recombinant bacterial genomes and an inactivated version of CcdA is inserted into a
linearised plasmid vector. A short extra sequence is added to the gene of interest that activates the antitoxin when the insertion occurs. This method ensures
orientation-specific gene insertion.
Genetically modified organism
A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with ...
s must be contained in a pre-defined area during
research
Research is creative and systematic work undertaken to increase the stock of knowledge. It involves the collection, organization, and analysis of evidence to increase understanding of a topic, characterized by a particular attentiveness to ...
.
Toxin-antitoxin systems can cause cell
suicide
Suicide is the act of intentionally causing one's own death.
Risk factors for suicide include mental disorders, physical disorders, and substance abuse. Some suicides are impulsive acts driven by stress (such as from financial or ac ...
in certain conditions, such as a lack of a lab-specific
growth medium
A growth medium or culture medium is a solid, liquid, or semi-solid designed to support the growth of a population of microorganisms or cells via the process of cell proliferation or small plants like the moss ''Physcomitrella patens''. Differe ...
they would not encounter outside of the controlled
laboratory
A laboratory (; ; colloquially lab) is a facility that provides controlled conditions in which scientific or technological research, experiments, and measurement may be performed. Laboratories are found in a variety of settings such as schools ...
set-up.
See also
*
Toxin-antitoxin database
*
Maternal effect dominant embryonic arrest (Medea)
References
External links
RASTA– Rapid Automated Scan for Toxins and Antitoxins in Bacteria
{{Good article
Plasmids
Non-coding RNA
Toxins
RNA-binding proteins