2
Mode of Action
The class I bacteriocin nisin and some of the class II bacteriocins have been
shown to be membrane-active peptides that destroy the integrity of the cytoplasmic membrane via the formation of membrane channels (Fig. 1). In doing
so, they alter the membrane permeability and therefore cause leakage of low
molecular mass metabolites or dissipate the proton motive force, thereby inhibiting energy production and biosynthesis of proteins or nucleic acids [1, 62].
Most bacteriocins produced by lactic acid bacteria display a bactericidal effect
on the sensitive cells, all or not resulting in cell lysis [63–67]. On the other hand,
other bacteriocins, such as lactocin 27 [68], leucocin A [69] and leuconocin S
[59] have been reported to act bacteriostatically. However, the designation of
lethal versus static effect can be dependent upon aspects of the assay system,
including the number of arbitrary units, the buffer or broth, the purity of the
inhibitor, and the indicator species and cell density used [1]. The mode of
action of numerous bacteriocins has been reported and, therefore, only a few of
them, representing the different classes are described in this section.
The class IA I lantibiotic nisin was shown to form ion-permeable channels in
the cytoplasmic membrane of susceptible cells, resulting in an increase in the
membrane permeability, disturbing the membrane potential and causing an
efflux of ATP, amino acids, and essential ions such as potassium and magnesium. Ultimately, the biosynthesis of macromolecules and energy production
are inhibited resulting in cell death. Nisin does not require a membrane receptor but requires an energized membrane for its activity, which appeared to be
dependent on the phospholipid composition of the membrane [67].
Lactococcin A can alter the permeability of the L. lactis cytoplasmic membrane leading to the loss of proton motive force and leakage of intracellular ions
and constituents [65, 70]. LcnA acts in a voltage independent manner on intact
cells or membrane vesicles, but not on liposomes suggesting that a specific
membrane receptor is required for LcnA recognition and action [65, 70].
Analogously, the antimicrobial activity of Las5 was not dependent on an
energized membrane, but required a trypsin-sensitive protein receptor to elicit
bactericidal action on protoplasted cells [64, 70].
The voltage independent activity of lactococcin B, similar to thiol-activated
toxins, was proposed to be dependent on the reduced state of its unique cysteine
residue on position 24 [71]. Recently, it was shown by means of protein engineering that the Cys-24 residue was not necessary for activity of lactococcin
B [28]. Lactococcin G is a novel lactococcal class IIB bacteriocin whose activity
depends on the action of two peptides [47]. The combination of the a and b
peptide dissipated the membrane potential, induced a dramatic decrease in the
cellular ATP level, and resulted in a rapid efflux of potassium [72].
The class IIA pediocins PA-1/AcH and JD were reported to exhibit their
bactericidal action at the cytoplasmic membrane and to cause a collapse of the
pH gradient and proton motive force [66, 73]. Furthermore, a leakage of K
+
, UVadsorbing materials, permeability to ONPG, and in some cases cell lysis,
although not attributed to the primary pediocin AcH action were observed [66,
Antimicrobial Peptides of Lactic Acid Bacteria: Mode of Action, Genetics and Biosynthesis
25
Mode of Action
The class I bacteriocin nisin and some of the class II bacteriocins have been
shown to be membrane-active peptides that destroy the integrity of the cytoplasmic membrane via the formation of membrane channels (Fig. 1). In doing
so, they alter the membrane permeability and therefore cause leakage of low
molecular mass metabolites or dissipate the proton motive force, thereby inhibiting energy production and biosynthesis of proteins or nucleic acids [1, 62].
Most bacteriocins produced by lactic acid bacteria display a bactericidal effect
on the sensitive cells, all or not resulting in cell lysis [63–67]. On the other hand,
other bacteriocins, such as lactocin 27 [68], leucocin A [69] and leuconocin S
[59] have been reported to act bacteriostatically. However, the designation of
lethal versus static effect can be dependent upon aspects of the assay system,
including the number of arbitrary units, the buffer or broth, the purity of the
inhibitor, and the indicator species and cell density used [1]. The mode of
action of numerous bacteriocins has been reported and, therefore, only a few of
them, representing the different classes are described in this section.
The class IA I lantibiotic nisin was shown to form ion-permeable channels in
the cytoplasmic membrane of susceptible cells, resulting in an increase in the
membrane permeability, disturbing the membrane potential and causing an
efflux of ATP, amino acids, and essential ions such as potassium and magnesium. Ultimately, the biosynthesis of macromolecules and energy production
are inhibited resulting in cell death. Nisin does not require a membrane receptor but requires an energized membrane for its activity, which appeared to be
dependent on the phospholipid composition of the membrane [67].
Lactococcin A can alter the permeability of the L. lactis cytoplasmic membrane leading to the loss of proton motive force and leakage of intracellular ions
and constituents [65, 70]. LcnA acts in a voltage independent manner on intact
cells or membrane vesicles, but not on liposomes suggesting that a specific
membrane receptor is required for LcnA recognition and action [65, 70].
Analogously, the antimicrobial activity of Las5 was not dependent on an
energized membrane, but required a trypsin-sensitive protein receptor to elicit
bactericidal action on protoplasted cells [64, 70].
The voltage independent activity of lactococcin B, similar to thiol-activated
toxins, was proposed to be dependent on the reduced state of its unique cysteine
residue on position 24 [71]. Recently, it was shown by means of protein engineering that the Cys-24 residue was not necessary for activity of lactococcin
B [28]. Lactococcin G is a novel lactococcal class IIB bacteriocin whose activity
depends on the action of two peptides [47]. The combination of the a and b
peptide dissipated the membrane potential, induced a dramatic decrease in the
cellular ATP level, and resulted in a rapid efflux of potassium [72].
The class IIA pediocins PA-1/AcH and JD were reported to exhibit their
bactericidal action at the cytoplasmic membrane and to cause a collapse of the
pH gradient and proton motive force [66, 73]. Furthermore, a leakage of K
+
, UVadsorbing materials, permeability to ONPG, and in some cases cell lysis,
although not attributed to the primary pediocin AcH action were observed [66,
Antimicrobial Peptides of Lactic Acid Bacteria: Mode of Action, Genetics and Biosynthesis
25