Colicin
Encyclopedia
A colicin is a type of bacteriocin
produced by and toxic to some strains of Escherichia coli
. Colicins are released into the environment to reduce competition from other bacterial strains. Colicins bind to outer membrane receptor
s, using them to translocate
to the cytoplasm or cytoplasmic membrane, where they exert their cytotoxic effect, including depolarisation of the cytoplasmic membrane, DNase activity, RNase activity, or inhibition of murein synthesis.
s that depolarize the cytoplasmic membrane, leading to dissipation of cellular energy. These colicins contain at least three domains: an N-terminal translocation domain responsible for movement across the outer membrane
and periplasmic space
; a central domain responsible for receptor recognition; and a C-terminal cytotoxic domain responsible for channel formation in the cytoplasmic membrane. One domain regulates the target and binds to the receptor on the sensitive cell. The second is involved with translocation, co-opting the machinery of the target cell. The third is the 'killing' domain and may produce a pore in the target cell membrane
, or act as a nuclease
to chop up the DNA
or RNA
of the target cell.
such as the porin
s OmpF, FepA, BtuB, Cir and FhuA; colicins have been classified according which receptors they bind to. The presence of specific periplasmic proteins, such as TolA, TolB, TolC
, or TonB, are required for translocation across the membrane. Cloacin DF13 is a bacteriocin that inactivates ribosomes by hydrolysing 16S RNA in 30S ribosomes at a specific site.
or vitamin B) but benefit by not being killed. Colicins exhibit a '1-hit killing kinetic' which doesn't necessarily mean a single molecule is sufficient to kill, but certainly that it only takes a small number. In his Nobel Laureate speech, Salvador E. Luria, 1969, speculated that colicins could only be this toxic by causing a domino effect
that destabilized the cell membrane. He was not entirely correct, but pore-forming colicins do de-polarize the membrane and thus eliminate the energy source for the cell. The colicins are highly effective toxin
s.
s. There are two general classes of colicinogenic plasmids, large, low-copy number plasmids, and small high copy number plasmids. The larger plasmids carry other genes as well as the colicin operon. The colicin operons are generally organized with several major gene
s. These include an immunity gene, a colicin structural gene, and a BRP (bacteriocin release protein), or lysis
, gene. The immunity gene is often produced constitutively, while the BRP is generally produced only as a read-through of the stop codon
on the colicin structural gene. The colicin itself is repressed by the SOS response
and may be regulated in other ways as well.
Research indicates that retaining the colicin plasmid is very important for cells that live with their relatives, because if a cell loses the immunity gene, it quickly becomes subject to destruction by circulating colicin. At the same time, colicin is only released from a producing cell by the use of the lysis protein, which results in that cell's death. This suicidal production mechanism would appear to be very costly, except for the fact that it is regulated by the SOS response
, which responds to significant DNA
damage. In short, colicin production may only occur in terminally-ill cells. Still these matters require further research. The Professor Kleanthous Research Group at the University of York
study colicins extensively as a model system for characterising and investigating protein-protein interactions and recognition.
BACTIBASE database is an open-access database for bacteriocins including colicins (view complete list).
Bacteriocin
Bacteriocins are proteinaceous toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain. They are typically considered to be narrow spectrum antibiotics, though this has been debated...
produced by and toxic to some strains of Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
. Colicins are released into the environment to reduce competition from other bacterial strains. Colicins bind to outer membrane receptor
TonB-dependent receptors
TonB-dependent receptors is a family of beta-barrel proteins from the outer membrane of Gram-negative bacteria. The TonB complex senses signals from outside the bacterial cell and transmits them via two membranes into the cytoplasm, leading to transcriptional activation of target genes.In...
s, using them to translocate
Translocase of the outer membrane
The translocase of the outer membrane is a complex of proteins found in the outer mitochondrial membrane of the mitochondria. Its function is to allow movement of proteins through this barrier and into the intermembrane space of the mitochondrion. Most of the proteins needed for mitochondrial...
to the cytoplasm or cytoplasmic membrane, where they exert their cytotoxic effect, including depolarisation of the cytoplasmic membrane, DNase activity, RNase activity, or inhibition of murein synthesis.
Structure
Channel-forming colicins (colicins A, B, E1, Ia, Ib, and N) are transmembrane proteinTransmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
s that depolarize the cytoplasmic membrane, leading to dissipation of cellular energy. These colicins contain at least three domains: an N-terminal translocation domain responsible for movement across the outer membrane
Outer membrane
The bacterial outer membrane is found in Gram-negative bacteria. Its composition is distinct from that of the cytoplasmic membrane - among other things, the outer leaflet of the membrane includes a complex lipopolysaccharide whose lipid portion acts as an endotoxin - and it is linked to the cell's...
and periplasmic space
Periplasmic space
The periplasmic space or periplasm is a space between the peptidoglycan cell wall and inner membrane of Gram-negative bacteria or the equivalent space outside the inner membrane of Gram-positive bacteria. It may constitute up to 40% of the total cell volume in Gram-negative species, and is...
; a central domain responsible for receptor recognition; and a C-terminal cytotoxic domain responsible for channel formation in the cytoplasmic membrane. One domain regulates the target and binds to the receptor on the sensitive cell. The second is involved with translocation, co-opting the machinery of the target cell. The third is the 'killing' domain and may produce a pore in the target cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
, or act as a nuclease
Nuclease
A nuclease is an enzyme capable of cleaving the phosphodiester bonds between the nucleotide subunits of nucleic acids. Older publications may use terms such as "polynucleotidase" or "nucleodepolymerase"....
to chop up the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
or RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
of the target cell.
Translocation
Most colicins are able to translocate the outer membrane by a two-receptor system, where one receptor is used for the initial binding and the second for translocation. The initial binding is to cell surface receptorsTonB-dependent receptors
TonB-dependent receptors is a family of beta-barrel proteins from the outer membrane of Gram-negative bacteria. The TonB complex senses signals from outside the bacterial cell and transmits them via two membranes into the cytoplasm, leading to transcriptional activation of target genes.In...
such as the porin
Porin
Porin may refer to:* Porin , a transmembrane protein* Porin , a Croatian grand Opera, first performed in 1897* Porin , the Croatian national music industry award, first awarded in 1994 and named after the opera...
s OmpF, FepA, BtuB, Cir and FhuA; colicins have been classified according which receptors they bind to. The presence of specific periplasmic proteins, such as TolA, TolB, TolC
Outer membrane efflux proteins
Outer membrane efflux protein family form trimericchannels that allow export of a variety of substrates in Gramnegative bacteria. Each member of this family is composed oftwo repeats...
, or TonB, are required for translocation across the membrane. Cloacin DF13 is a bacteriocin that inactivates ribosomes by hydrolysing 16S RNA in 30S ribosomes at a specific site.
Resistance
Because they target specific receptors and use specific translocation machinery, cells can make themselves resistant to the colicin by repressing or deleting the genes for these proteins. Such resistant cells may suffer the lack of a key nutrient (such as ironIron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
or vitamin B) but benefit by not being killed. Colicins exhibit a '1-hit killing kinetic' which doesn't necessarily mean a single molecule is sufficient to kill, but certainly that it only takes a small number. In his Nobel Laureate speech, Salvador E. Luria, 1969, speculated that colicins could only be this toxic by causing a domino effect
Domino effect
The domino effect is a chain reaction that occurs when a small change causes a similar change nearby, which then will cause another similar change, and so on in linear sequence. The term is best known as a mechanical effect, and is used as an analogy to a falling row of dominoes...
that destabilized the cell membrane. He was not entirely correct, but pore-forming colicins do de-polarize the membrane and thus eliminate the energy source for the cell. The colicins are highly effective toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
s.
Genetic organisation
Virtually all colicins are carried on plasmidPlasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...
s. There are two general classes of colicinogenic plasmids, large, low-copy number plasmids, and small high copy number plasmids. The larger plasmids carry other genes as well as the colicin operon. The colicin operons are generally organized with several major gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s. These include an immunity gene, a colicin structural gene, and a BRP (bacteriocin release protein), or lysis
Lysis
Lysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....
, gene. The immunity gene is often produced constitutively, while the BRP is generally produced only as a read-through of the stop codon
Stop codon
In the genetic code, a stop codon is a nucleotide triplet within messenger RNA that signals a termination of translation. Proteins are based on polypeptides, which are unique sequences of amino acids. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide...
on the colicin structural gene. The colicin itself is repressed by the SOS response
SOS response
The SOS response is a global response to DNA damage in which the cell cycle is arrested and DNA repair and mutagenesis are induced. The SOS uses the RecA protein . The RecA protein, stimulated by single-stranded DNA, is involved in the inactivation of the LexA repressor thereby inducing the response...
and may be regulated in other ways as well.
Research indicates that retaining the colicin plasmid is very important for cells that live with their relatives, because if a cell loses the immunity gene, it quickly becomes subject to destruction by circulating colicin. At the same time, colicin is only released from a producing cell by the use of the lysis protein, which results in that cell's death. This suicidal production mechanism would appear to be very costly, except for the fact that it is regulated by the SOS response
SOS response
The SOS response is a global response to DNA damage in which the cell cycle is arrested and DNA repair and mutagenesis are induced. The SOS uses the RecA protein . The RecA protein, stimulated by single-stranded DNA, is involved in the inactivation of the LexA repressor thereby inducing the response...
, which responds to significant DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
damage. In short, colicin production may only occur in terminally-ill cells. Still these matters require further research. The Professor Kleanthous Research Group at the University of York
University of York
The University of York , is an academic institution located in the city of York, England. Established in 1963, the campus university has expanded to more than thirty departments and centres, covering a wide range of subjects...
study colicins extensively as a model system for characterising and investigating protein-protein interactions and recognition.
BACTIBASE database is an open-access database for bacteriocins including colicins (view complete list).
External links
- Molecular mechanisms of colicin evolution pdf
- The newly characterized colicin Y provides evidence of positive selection in pore-former colicin diversification
- Colicin OPM database
- 3D interactive pages about colicins
- Transport Classification Database listing for colicin
- Protein Data Bank colicin listing