BACTERIOCIN

Introduction
Bacteriocins are proteinaceous toxins 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. He was involved in the
process of searching for ways to kill bacteria, which also resulted
in the development of antibiotics 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.
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 , the
microcins, 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[5]or
warnericin. In fact, one of the oldest known so-called colicins was
called colicin V and is now know as microcin V. It is much smaller
and produced and secreted in a different manner than the classic
colicins. The bacteriocins of lactic acid-fermenting bacteria are
called lantibiotics. This naming system is problematic for a
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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.
Methods 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 bacteriocins are small peptide inhibitors and
include nisin.

Class II bacteriocins
The class II bacteriocins are small heat-stable proteins. The
action of Class IIa bacteriocins seems to involve disruption of
mannose transport into target cells. Class IIb bacteriocins form
pores in the membranes of target cells and disrupt the proton
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gradient of target cells. Other bacteriocins can be grouped
together as Class IIc. These have a wide range of effects on
membrane permeability, cell wall formation and pheromone
actions of target cells.

Class III bacteriocins

Large, heat-labile protein bacteriocins.

Databases
Two databases of bacteriocins are available: BAGEL and
BACTIBASE.
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 antibiotic
use may allow opportunistic pathogenic bacteria to invade the
human body.
Bacteriocins have also been suggested as a cancer
treatmentThey 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
In the long quest for medical applications, bacteriocins have also
been tested as AIDS drugs

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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 Petri dishes, 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.

Bacteriocins by class
•Class I
•Class IIa
•Class IIb
•Class IIc
•Class III

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Bacteriocins by name
agrocin alveicin carnocin colicin curvaticin divercin enterocin
enterolysin epidermin erwiniocin glycinecin halocin lactococin
lacticin leucoccin mesentericin nisin pediocin plantaricin sakacin
subtilin sulfolobicin vibriocin warnerin
Chemistry of bacteriocin
Bacteriocins are proteinaceous toxins given off by bacteria
to inhibit the growth of similar bacterial strain(s). E. coli
bacteriocins are called colicins.
The bacteriocins of lactic acid-fermenting bacteria are well
studied because of the commercial use of these bacteria in the
food industry for making dairy products such as cheese.
Bacteriocins are classified according to their extent of
posttranslational modification. The lantibiotics are a class of more
extensively modified bacteriocins, also called Class I. Bacteriocins
for which disulfide bonds are the only modification to the peptide
are Class II bacteriocins. Most bacteriocins are biologically active
single-chain peptides. Some are only active as partners with a
second peptide (see Class IIb, below).
Nisin and epidermin are members of a family of lantibiotics
that bind to a cell wall precursor lipid component of target bacteria
and disrupt cell wall production. The duramycin family of
lantibiotics binds phosphoethanolamine in the membranes of its
target cells and seem to disrupt several physiological functions.
The action of Class IIa bacteriocins seems to involve
disruption of mannose transport into target cells. Class IIb
bacteriocins form pores in the membranes of target cells and
disrupt the proton gradient of target cells. Other bacteriocins can
be grouped together as Class IIc. These have a wide range of
effects on membrane permeability, cell wall formation and
pheromone actions of target cells.
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 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 antibiotic
use may allow oportunistic pathogenic bacteria to invade the
human body.
To demonstrate their production, technicians stab inoculate
multiple strains on separate multiple nutrient agar Petri dishes,
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.
Class II bacteriocins are a class of small peptides that inhibit the
growth of various bacteria.
Many Gram-positive bacteria produce ribosomally
synthesized antimicrobial peptides, termed bacteriocins. One
important and well studied class of bacteriocins is the class IIa or
pediocin-like bacteriocins produced by lactic acid bacteria. All
class IIa bacteriocins are produced by food-associated strains,
isolated from a variety of food products of industrial and natural
origins, including meat products, dairy products and vegetables.
Class IIa bacteriocins are all cationic, display anti-Listeria activity,
and kill target cells by permeabilizing the cell membrane[1][2][3].
Class IIa bacteriocins contain between 37 and 48 residues[4].
Based on their primary structures, the peptide chains of class IIa
bacteriocins may be divided roughly into two regions: a
hydrophilic, cationic and highly conserved N-terminal region, and
a less conserved hydrophobic/amphiphilic C-terminal region. The
N-terminal region contains the conserved Y-G-N-G-V/L 'pediocin
box' motif and two conserved cysteine residues joined by a
disulfide bridge. It forms a three-stranded antiparallel beta-sheet
supported by the conserved disulfide bridge. This cationic N-
terminal beta-sheet domain mediates binding of the class IIa
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bacteriocin to the target cell membrane. The C-terminal region
forms a hairpin-like domain that penetrates into the hydrophobic
part of the target cell membrane, thereby mediating leakage
through the membrane. The two domains are joined by a hinge,
which enables movement of the domains relative to each other.
Some proteins known to belong to the class IIa bacteriocin family
are listed below:
•Pediococcus acidilactici pediocin PA-1.
•Leuconostoc mesenteroides mesentericin Y105.
•Carnobacterium piscicola carnobacteriocin B2.
•Lactobacillus sakei sakacin P.
•Enterococcus faecium enterocin A.
•Enterococcus faecium enterocin P.
•Leuconostoc gelidum leucocin A.
•Lactobacillus curvatus curvacin A.
•Listeria innocua listeriocin 743A.

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 REFERENCES

1. Ennahar S, Sonomoto K, Ishizaki A (1999). "Class IIa bacteriocins

from lactic acid bacteria: antibacterial activity and food
preservation". J. Biosci. Bioeng. 87
2. Farkas-Himsley H (1980). "Bacteriocins--are they broad-spectrum
antibiotics?". J. Antimicrob. Chemother. 6 (4): 424–6.
doi:10.1093/jac/6.4.424. PMID 7430010.
3. Gratia A (1925). "Sur un remarquable example d'antagonisme entre
deux souches de colibacille". Compt. Rend. Soc. Biol. 93: 1040–2.
4. Gratia JP (October 2000). "André Gratia: a forerunner in microbial
and viral genetics". Genetics 156 (2): 471–6. PMID 11014798.
http://www.genetics.org/cgi/pmidlookup?view=long&pmid=11014
798.