Bacteriocin
Encyclopedia
Bacteriocins are protein
aceous toxin
s produced by bacteria
to inhibit the growth of similar or closely related bacterial strain(s). They are typically considered to be narrow spectrum antibiotics, though this has been debated. They are phenomenologically analogous to yeast
and paramecium
killing factors, and are structurally, functionally, and ecologically diverse.
Bacteriocins were first discovered by A. Gratia in 1925. A Gratia was given the credit for the discovery but many scientists such as Christopher Sobieralski believe that Bacteriocins were actually discovered in a microcosm living on Garrets fingernails He was involved in the process of searching for ways to kill bacteria, which also resulted in the development of antibiotic
s and the discovery of bacteriophage
, all within a span of a few years. He called his first discovery a colicine because it killed E. coli.
, and the bacteriocins from Archaea
. The bacteriocins from E. coli are called colicins (formerly called 'colicines,' meaning 'coli killers'). They are the longest studied bacteriocins. They are a diverse group of bacteriocins and do not include all the bacteriocins produced by E. coli. For example the bacteriocins produced by Staphylococcus warneri
are called as warnerin or warnericin. In fact, one of the oldest known so-called colicins was called colicin V and is now known as microcin V. It is much smaller and produced and secreted in a different manner than the classic colicins.
This naming system is problematic for a number of reasons. First, naming bacteriocins by what they putatively kill would be more accurate if their killing spectrum were contiguous with genus or species designations. The bacteriocins frequently possess spectra that exceed the bounds of their named taxa and almost never kill the majority of the taxa for which they are named. Further, the original naming is generally derived not from the sensitive strain the bacteriocin kills, but instead the organism that produces the bacteriocin. This makes the use of this naming system a problematic basis for theory; thus the alternative classification systems.
Bacteriocins that contain the modified amino acid Lanthionine
as part of their structure are called lantibiotics
.
One method of classification fits the bacteriocins into Class I, Class IIa/b/c, and Class III.
are small peptide inhibitors and include nisin
and other lantibiotics.
formation and pheromone
actions of target cells.
use may allow opportunistic pathogenic bacteria to invade the human body.
Bacteriocins have also been suggested as a cancer treatment. They have shown distinct promise as a diagnostic agent for some cancers, but their status as a form of therapy remains experimental and outside the main thread of cancer research. Partly this is due to questions about their mechanism of action and the presumption that anti-bacterial agents have no obvious connection to killing mammalian tumor cells. Some of these questions have been addressed, at least in part.
Bacteriocins (which?) were tested as AIDS drugs (around 1990) but not progressed beyond in-vitro tests on cell lines.
To demonstrate their production, technicians stab inoculate multiple strains on separate multiple nutrient agar
Petri dish
es, incubate at 30 °C for 24 h., overlay each plate with one of the strains
(in soft agar), incubate again at 30 °C for 24 h. After this process, the presence of bacteriocins can be inferred if there are zones of growth inhibition around stabs. This is the simplest and least sensitive way. It will often mistake phage
for bacteriocins.
Some methods prompt production with UV radiation, Mitomycin C, or heat shock
. UV radiation and Mitomycin C are used because the DNA damage they produce stimulates the SOS response
. Cross streaking may be substituted for lawns. Similarly, production in broth may be followed by dripping the broth on a nascent bacterial lawn, or even filtering it. Precipitation (ammonium sulfate
) and some purification (e.g. column or HPLC) may help exclude lysogenic and lytic phage
from the assay.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
aceous toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
s produced by bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
to inhibit the growth of similar or closely related bacterial strain(s). They are typically considered to be narrow spectrum antibiotics, though this has been debated. They are phenomenologically analogous to yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
and paramecium
Paramecium
Paramecium is a group of unicellular ciliate protozoa, which are commonly studied as a representative of the ciliate group, and range from about 0.05 to 0.35 mm in length. Simple cilia cover the body, which allow the cell to move with a synchronous motion at speeds of approximately 12 body...
killing factors, and are structurally, functionally, and ecologically diverse.
Bacteriocins were first discovered by A. Gratia in 1925. A Gratia was given the credit for the discovery but many scientists such as Christopher Sobieralski believe that Bacteriocins were actually discovered in a microcosm living on Garrets fingernails He was involved in the process of searching for ways to kill bacteria, which also resulted in the development of antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s and the discovery of bacteriophage
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
, all within a span of a few years. He called his first discovery a colicine because it killed E. coli.
Classification of bacteriocins
Bacteriocins are categorized in several ways, including producing strain, common resistance mechanisms, and mechanism of killing. There are several large categories of bacteriocin which are only phenomenologically related. These include the bacteriocins from gram-positive bacteria, the colicins, the microcinsMicrocins
Microcins are very small bacteriocins, composed of a relatively few peptides. For this reason, they are distinct from their larger protein cousins. The classic example is microcin V, of E. coli....
, and the bacteriocins from Archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
. The bacteriocins from E. coli are called colicins (formerly called 'colicines,' meaning 'coli killers'). They are the longest studied bacteriocins. They are a diverse group of bacteriocins and do not include all the bacteriocins produced by E. coli. For example the bacteriocins produced by Staphylococcus warneri
Staphylococcus warneri
Staphylococcus warneri is a member of the bacterial genus Staphylococcus, consisting of Gram-positive bacteria with spherical cells appearing in clusters. It is coagulase-negative and is a common commensal organism found as part of the skin flora on humans and animals. Like other coagulase-negative...
are called as warnerin or warnericin. In fact, one of the oldest known so-called colicins was called colicin V and is now known as microcin V. It is much smaller and produced and secreted in a different manner than the classic colicins.
This naming system is problematic for a number of reasons. First, naming bacteriocins by what they putatively kill would be more accurate if their killing spectrum were contiguous with genus or species designations. The bacteriocins frequently possess spectra that exceed the bounds of their named taxa and almost never kill the majority of the taxa for which they are named. Further, the original naming is generally derived not from the sensitive strain the bacteriocin kills, but instead the organism that produces the bacteriocin. This makes the use of this naming system a problematic basis for theory; thus the alternative classification systems.
Bacteriocins that contain the modified amino acid Lanthionine
Lanthionine
Lanthionine is a nonproteinogenic amino acid with the chemical formula . As the monosulfide analog of cystine, lanthionine is composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage...
as part of their structure are called lantibiotics
Lantibiotics
Lantibiotics are a class of peptide antibiotics that contain the characteristic polycyclic thioether amino acids lanthionine or methyllanthionine, as well as the unsaturated amino acids dehydroalanine and 2-aminoisobutyric acid....
.
Methods of classification
Alternative methods of classification include: method of killing (pore forming, dnase, nuclease, murein production inhibition, etc.), genetics (large plasmids, small plasmids, chromosomal), molecular weight and chemistry (large protein, polypeptide, with/without sugar moiety, containing atypical amino acids like lanthionine) and method of production (ribosomal, post ribosomal modifications, non-ribosomal).One method of classification fits the bacteriocins into Class I, Class IIa/b/c, and Class III.
Class I bacteriocins
The class I bacteriocinsLantibiotics
Lantibiotics are a class of peptide antibiotics that contain the characteristic polycyclic thioether amino acids lanthionine or methyllanthionine, as well as the unsaturated amino acids dehydroalanine and 2-aminoisobutyric acid....
are small peptide inhibitors and include nisin
Nisin
Nisin is a polycyclic antibacterial peptide with 34 amino acid residues used as a food preservative. It contains the uncommon amino acids lanthionine , methyllanthionine , didehydroalanine and didehydroaminobutyric acid . These unusual amino acids are introduced by posttranslational modification...
and other lantibiotics.
Class II bacteriocins
The class II bacteriocins are small heat-stable proteins. The class IIa bacteriocins (pediocin-like bacteriocins) are the largest subgroup and contain an N-terminal consensus sequence -Tyr-Gly-Asn-Gly-Val-Xaa-Cys across this group. The C-terminal is responsible for species-specific activity, causing cell-leakage by permeabilizing the target cell wall. Class IIa bacteriocins have a large potential for use in food preservation as well medical applications, due to their strong antilisterial activity, and broad range of activity. The class IIb bacteriocins (two-peptide bacteriocins) require two different peptides for activity. Other bacteriocins can be grouped together as Class IIc (circular bacteriocins). These have a wide range of effects on membrane permeability, cell wallCell wall
The cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...
formation and pheromone
Pheromone
A pheromone is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting outside the body of the secreting individual to impact the behavior of the receiving individual...
actions of target cells.
Medical significance
Bacteriocins are of interest in medicine because they are made by non-pathogenic bacteria that normally colonize the human body. Loss of these harmless bacteria following antibioticAntibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
use may allow opportunistic pathogenic bacteria to invade the human body.
Bacteriocins have also been suggested as a cancer treatment. They have shown distinct promise as a diagnostic agent for some cancers, but their status as a form of therapy remains experimental and outside the main thread of cancer research. Partly this is due to questions about their mechanism of action and the presumption that anti-bacterial agents have no obvious connection to killing mammalian tumor cells. Some of these questions have been addressed, at least in part.
Bacteriocins (which?) were tested as AIDS drugs (around 1990) but not progressed beyond in-vitro tests on cell lines.
Production
There are many ways to demonstrate bacteriocin production, depending on the sensitivity and labor intensiveness desired.To demonstrate their production, technicians stab inoculate multiple strains on separate multiple nutrient agar
Agar
Agar or agar-agar is a gelatinous substance derived from a polysaccharide that accumulates in the cell walls of agarophyte red algae. Throughout history into modern times, agar has been chiefly used as an ingredient in desserts throughout Asia and also as a solid substrate to contain culture medium...
Petri dish
Petri dish
A Petri dish is a shallow glass or plastic cylindrical lidded dish that biologists use to culture cells or small moss plants. It was named after German bacteriologist Julius Richard Petri, who invented it when working as an assistant to Robert Koch...
es, incubate at 30 °C for 24 h., overlay each plate with one of the strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...
(in soft agar), incubate again at 30 °C for 24 h. After this process, the presence of bacteriocins can be inferred if there are zones of growth inhibition around stabs. This is the simplest and least sensitive way. It will often mistake phage
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
for bacteriocins.
Some methods prompt production with UV radiation, Mitomycin C, or heat shock
Heat shock
In biochemistry, heat shock is the effect of subjecting a cell to a higher temperature than that of the ideal body temperature of the organism from which the cell line was derived.-Heat shock response:...
. UV radiation and Mitomycin C are used because the DNA damage they produce stimulates 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...
. Cross streaking may be substituted for lawns. Similarly, production in broth may be followed by dripping the broth on a nascent bacterial lawn, or even filtering it. Precipitation (ammonium sulfate
Ammonium sulfate
Ammonium sulfate , 2SO4, is an inorganic salt with a number of commercial uses. The most common use is as a soil fertilizer. It contains 21% nitrogen as ammonium cations, and 24% sulfur as sulfate anions...
) and some purification (e.g. column or HPLC) may help exclude lysogenic and lytic phage
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
from the assay.
Bacteriocins by name
- acidocin
- actagardine
- agrocin
- alveicin
- aureocin
- carnocin
- carnocyclin
- colicinColicinA 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...
- curvaticin
- divercin
- duramycin
- enterocin
- enterolysin
- epidermin/gallidermin
- erwiniocin
- glycinecin
- halocinHalocinHalocins are bacteriocins produced by halophilic Archaea and a type of archaeocin.Since their discovery in 1982, halocins have been demonstrated to be diverse in a similar ways as the other bacteriocins. Some are large proteins, some small polypeptides...
- haloduracin
- lactococin
- lacticin
- leucoccin
- macedocin
- mersacidin
- mesentericin
- microbisporicin
- mutacin
- nisinNisinNisin is a polycyclic antibacterial peptide with 34 amino acid residues used as a food preservative. It contains the uncommon amino acids lanthionine , methyllanthionine , didehydroalanine and didehydroaminobutyric acid . These unusual amino acids are introduced by posttranslational modification...
- paenibacillin
- planosporicin
- pediocin
- pentocin
- plantaricin
- reutericin
- sakacinSakacinSakacins are bacteriocins produced by Lactobacillus sakei. They are often clustered with the other lactic acid bacteriocins. The best known sakacins are sakacin A, G, K, P, and Q. In particular, sakacin A and P have been well characterized....
- salivaricin
- subtilin
- sulfolobicin
- thuricin 17
- trifolitoxin
- variacin
- vibriocinVibriocinVibriocins are a group of bacteriocins produced by, and active against, gram-negative bacteria in the genus Vibrio. They were first revealed in 1962, considerably after the original bacteriocins, the colicins, which were discovered in 1925....
- warnericin
- warnerin