Bacteriocins
R Lagos, Universidad de Chile, Santiago, Chile
© 2013 Elsevier Inc. All rights reserved.
Glossary
ABC exporter Also called type I exporter, corresponds to
membrane proteins that participate in the export of
metabolites, peptides, or proteins in a specific manner
(dedicated exporter, energy driven by adenosine
triphosphate (ATP) hydrolysis), with a characteristic
domain called ABC (ATP-binding cassette).
Pathogenicity island Part of a bacterial genome acquired
by horizontal transfer encoding genes involved in
pathogenesis.
Quorum sensing Communication between bacteria given
by molecules secreted by the cells that coordinate the
Introduction
Bacteriocins are a large family of ribosomally synthesized pro­
teinaceous toxins produced by bacteria and Archaea that have
antimicrobial activity against bacteria closely related to the
producer strain. The term ‘bacteriocin’ was introduced to
denote a toxic protein or peptide produced by any type of
bacteria that is active on related bacteria but does not harm
the producing cell. This expression was inspired by analogy
with colicin, the first bacteriocin described that was produced
by Escherichia coli. In this case, the suffix cin was added to the
producing species, such as in the case of pyocins (from
Pseudomonas pyocyanea, now P. aeruginosa) and cloacins
(Enterobacter cloacae), to mention a few. The genus name has
also been employed to name bacteriocins, for instance klebi­
cins (from Klebsiella), lactococcins (from Lactococcus),
staphylococcins (from Staphylococcus), and many others.
Although bacteriocins present toxic activities on bacteria, they
should not be confused with ‘toxins’ (exotoxins), a term that is
reserved for proteins produced by bacteria that have a toxic
effect on an animal host through specific cytotoxic action on
specialized cells (e.g., hemolysins and cytolysins).
Mechanisms of Action
The mechanisms by which bacteriocins exert antimicrobial
activity are diverse. The most common are the disruption of
the cytoplasmic membrane by pore-forming structures, cell-
wall interference by inhibition of peptidoglycan synthesis,
nucleases production (DNases or RNases), nucleic acid
metabolism interference by inhibition of gyrase or RNA poly­
merase, and others. In all these cases, the bacteriocin has to
reach the target in the cell. In the case of Gram-negative bac­
teria, the target can be located at the periplasm, the cytoplamic
membrane, or at the cytoplasm, and it is reached after a
receptor-recognition step. The main two uptakes utilized by
Gram-negative bacteriocins are outer membrane proteins
Brenner’s Encyclopedia of Genetics, 2nd edition, Volume 1 doi:10.1016/B978-0-12-374984-0.00291-6
expression of certain genes according to the bacterial
population density.
Salmochelin Enterochelin (cyclic trimer of N-(2,3­
dihydroxybenzoyl)-L-serine) glycosylated with one or two
glucose molecules; a siderophore produced by Salmonella
sp. and other pathogenic strains.
Siderophore Compounds synthesized and secreted by
microorganisms that chelate iron with high affinity. The
siderophore–iron complex is recognized by specific
receptors for an efficient internalization and release of
iron.
associated to the TonB or Tol systems, both used for important
biological functions involved in the import of molecules (nat­
ural ligands) such as vitamin B12, iron bound to siderophores,
and others. Receptor recognition is key for the antibacterial
activity, and is the reason why the Gram-negative bacteriocins
in general have a narrow host range: they are active only on
strains having the specific receptors. This is in contrast with
classic antibiotics, which are directed toward a broader spec­
trum of bacteria. The situation as regards Gram-positive
bacteria is different: in this case, the outer membrane barrier
does not exist, and the cell wall allows the passage of relatively
large molecules; hence, absorption shows little specificity.
However, there is a family of Gram-positive bacteriocins that
needs specific interaction with receptor proteins from the cyto­
plasmic membrane, and consequently has a very narrow
spectrum of activity, whereas there are cationic bacteriocins
that present an initial interaction with anionic cell-surface
polymers (such as teichoic acid, lipoteichoic acid, and anionic
phospholipids), which results in a class of bacteriocins that are
active against a broad variety of bacteria belonging to different
genera.
Immunity
How does the producing strain avoid killing itself? There is a
self-protection mechanism that prevents the toxic effect of the
bacteriocin on the producing strain, a process called immunity
(although it is very different from phage immunity). This protec­
tion is achieved by specific mechanisms that block the action of
the bacteriocins. For example, the immunity for pore-forming
bacteriocins is given by membrane proteins that neutralize the
bacteriocin by a direct interaction, or by an interaction with
proteins needed for the insertion of the bacteriocin into the
membrane; the immunity to bacteriocins with nuclease activity
(or other activities) is given by association of the immunity
protein with the bacteriocin, forming an inactive complex.
Immunity should not be confused with resistance. Although,
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278 Bacteriocins
in both cases, there is no toxic effect after the exposure to the
bacteriocin, the immunity corresponds to a specific mechanism
to counteract the toxic effect, whereas the resistance results, for
example, because of the lack of a specific receptor on the target
cell, so the bacteriocin cannot reach the objective.
Bacteriocin Produced by Gram-Negative Bacteria
Two main groups can be distinguished: colicins or colicins-
like bacteriocins, which are heat labile and have a high mole­
cular weight (>20 000); and small (<10 000), heat-resistant
bacteriocins, which due to their small size are called
microcins.
Colicin and colicin-like bacteriocins are typically encoded
in plasmids and the genetic organization is very simple, with
only three components: the colicin, the immunity, and the
lysis genes. The production of colicins occurs under stress
conditions: they are induced by the SOS system, in which
not only the expression of the colicin is induced but also the
lysis gene, which in turn causes cellular lysis, with the libera­
tion of the bacteriocin. Hence, the release of colicins to the
extracellular space implies bacterial death. Another salient
feature of colicins is that they have three domains that are
related with the steps necessary for antibacterial activity:
reception (central domain), translocation (N terminal), and
toxicity (C terminal). The first is needed for binding to the
receptor at the outer membrane; the second for translocation
across the cell envelope; and the third for the killing. In this
process, colicins would unfold, and maintain an extended
conformation across the cell envelope in contact with the
receptor. Typical pore-forming colicins are colicins E1, A, B,
K, Ia, Ib, and N; those with DNase activity are E2, E7, and E9;
those with RNase activity (transfer RNA (tRNA) and 16S RNA)
are D, E5, E3, E4, and E6; and that blocking peptidoglycan
synthesis is colicin M. It is worth mentioning that most of the
plasmid vectors utilized today carry the replication origin of
plasmid ColE1, which encodes for colicin E1.
Microcins can be either plasmid or chromosomally
encoded. They are subdivided into very small (mass <5000)
microcins that are highly modified, the most representative
microcins being B17 (inhibits DNA gyrase), J25 (inhibits RNA
polymerase), and C7 (affects protein synthesis), and microcins
with a mass between 5 and 10 000 that may be or not
posttranslationally modified. Microcins E492 (pore forming),
H47, and M are modified at the C-terminal with
salmochelin-like molecules, whereas microcin L and colicin V
belong to the non-modified group. Microcins are heat resistant,
usually induced in the stationary phase, and, in contrast to
colicins, they are exported to the extracellular space by specific
ABC (ATP-binding cassette) exporters encoded in the microcin
gene clusters; consequently, the liberation of microcins does
not result in cellular death. In this regard, they are similar to
some bacteriocins produced by Gram-positive bacteria, as well
as in other characteristics such as thermostability, hydrophobi­
city, resistance to extreme pH, and resistance to some proteases.
Microcins M and H47 can be chromosomally encoded into
pathogenicity islands.
Bacteriocins Produced by Gram-Positive Bacteria
There is a great diversity of bacteriocins produced by Gram-
positive microorganisms. Interestingly, the term ‘bacteriocin’ is
commonly associated with those produced by Gram-positive
bacteria, in contrast to those produced by Gram-negative bac­
teria, which are mainly identified as ‘colicins’ and ‘microcins’.
The main difference between bacteriocins from Gram-positive
and colicins from Gram-negative bacteria are: their production is
not lethal because they are secreted through specific or
sec-dependent export pathways; and some Gram-positive bac­
teria have evolved bacteriocin-specific regulation (such as
quorum sensing), in contrast to Gram-negative bacteriocins
that are under the host’s regulatory networks. Gram-positive
bacteriocins have been classified into four groups: class I,
posttranslationally modified bacteriocins that contain modified
amino acids, such as lanthionine, methyllanthionine, and dehy­
drated amino acids, and that are collectively known as
lantibiotics; class II, small (<10 000) heat-stable, non-modified
bacteriocins; class III, large (>10 000) heat-labile bacteriocins;
and class IV, complex bacteriocins, carrying lipid or carbohydrate
moieties. Class I, II, and III Gram-positive bacteriocins are
further subdivided according to other characteristics. The most
studied are class I and class II, many of them being produced by
lactic acid bacteria (LAB), also known as LAB bacteriocins.
Lantibiotics (or class I) are bacteriocins toxic on a broad
range of Gram-positive bacteria, encoded in complex genetic
systems located either in plasmids or in the chromosome in
which are present the export and maturation genes needed for
the specific exporters and for posttranslational modification.
Lantibiotic production is regulated by a strategy called ‘quorum
sensing’, in which the concentration of the bacteriocin functions
as a signal molecule that evaluates cellular density, and after
certain point induces its own expression. Lantibiotics are synthe­
sized as precursor peptides, with an N-terminal leader peptide
that is processed. Several lantibiotics are produced by food-grade
bacteria, which made them suitable as food preservatives. The
most representative member of this group is nisin, a
pore-forming bacteriocin with a broad variety of targets,
among them strains of Lactococcus, Streptococcus, Staphylococcus,
Listeria, Mycobacterium, Bacillus, and Clostridium. Nisin would use
Lipid II, a peptidoglycan precursor, as a docking molecule for
binding to specific membranes. Other lantibiotics are epider­
min, gallidermin, cytolysin, and cynnamicin.
Class II bacteriocins encompass hydrophobic thermostable
small non-modified bacteriocins produced by Lactobacillus,
Lactococcus, Pediococcus, and Enterococcus among other strains.
They function either as a single peptide or may require two or
more components for the toxic activity. The bacteriocin is
synthesized as a precursor that is processed while being
exported by ABC exporters. Pediocins, listeriocins, lactococcins,
and enterocins belong to this group.
Bacteriocins Produced by Archaea
The proper name for bacteriocins produced by Archaea is
‘archaeocins’. The best-characterized member are the halocins,
produced by halobacteria. They are produced mainly in the
stationary phase.

Ecological Significance of Bacteriocins
Although it is evident that bacteriocins serve some functions
in bacterial communities, many studies have turned out to
be inconclusive or contradictory. However, new develop­
ments point to the role of bacteriocins as regulators of
bacterial populations. The rock–paper–scissor model (pair
interactions between resistant, sensitive, and producing
strains) lends support to the hypothesis that bacteriocins
may promote rather than eliminate bacterial diversity in the
ecosystem.
Applications
Application of bacteriocins in food preservation has been suc­
cessful: currently, the use of the lantibiotic nisin has been
approved by the Food and Drug Administration (FDA) as a
food preservative. In this regard, LAB bacteriocins would be
advantageous because they are produced by bacteria that have
been in food for centuries without producing any harm.
Pharmaceutical applications for epidermin and gallidermin
are been explored for acne. In another line of research, bacter­
iocins may be used as structural models in the design of new
antibiotics, specifically if the toxic part of the molecule has
been identified. The strategies used by bacteriocins may also
be used as a model, such as the case of the Trojan horse strategy,
in which the host is deceived by molecules that resemble
normal compounds required for cellular growth. This is the
Bacteriocins 279
case of microcin E492, which is modified at the C-terminal end
with a salmochelin-like molecule that is recognized by side­
rophore–iron receptors, and allow bacteriocin translocation to
the target cell. Eventually, this knowledge may be used in the
design of new antibiotics that need to cross the
outer-membrane barrier. Microcin E492 has also antitumor
properties that can be exploited in cancer therapy.
See also: Col Factors; Plasmids; Quorum Sensing; SOS Repair.
Further Reading
Cascales E, Buchanan SK, Duché D, et al., (2007) Colicin biology. Microbiology and
Molecular Biology Reviews 71: 158–229.
Gillor O, Nigro LM, and Riley MA (2005) Genetically engineered bacteriocins and their
potential as the next generation of antimicrobials. Current Pharmaceutical Design 11:
1067–1075.
Riley MA and Chavan MA (eds.) (2007) Bacteriocins: Ecology and Evolution. Berlin;
Heidelberg: Springer-Verlag.
Riley MA and Gillor O (eds.) (2007) Research and Applications in Bacteriocins. Norfolk:
Horizon Bioscience.
Riley MA and Wertz JE (2002) Bacteriocins: Evolution, ecology, and application. Annual
Review of Microbiology 56: 117–137.
Relevant Websites
http://bagel2.molgenrug.nl – Bagel2: The bacteriocin mining tool. BAGEL2 is a
web-based bacteriocin mining tool.