by members of the Enterobacteriaceae [78]. Selection of spontaneous mutants
for insensitivity to the peptide antibiotic microcin 25 led to the isolation of five
categories of mutations, located in the fhuA, exb, tonB and sbmA genes [79]. The
latter three are all proteins of the cytoplasmic membrane, whereas FhuA is a
multifunctional protein of the outer membrane. [78, 79]. The region of FhuA,
which is important of microcin 25 interaction has subsequently been mapped
[80]. Several of these mutants showed an additional resistance to colicin M,
colicin B, and to bacteriophages T1 and F80 [79]. These results indicate that
microcin 25 interacts with an extracellular domain of the multifunctional
receptor FhuA, and is imported through the TonB pathway and the SbmA
protein [79].
In conclusion, pore formation in the cytoplasmic membrane seems to be a
common mode of action of those LAB bacteriocins for which the mode of
action has been determined. Some of the class II bacteriocins (lactococcin A, B,
G and lactacin F) require a specific receptor molecule for adsorption, whereas
nisin also acts on liposomes and exerts a receptor-independent action. Differences between narrow or wide host-range bacteriocins seem to be correlated
with this aspect of a specific receptor, needed for activity. However, which
bacteriocin domains confer binding specificities to lipid, protein, or reactive
groups remain to be elucidated.
3
Genetics of Bacteriocins Produced by Lactic Acid Bacteria
3.1
Nisin, the Most Prominent Member of the Class IA I Lantibiotics
The class I bacteriocins, the so-called lantibiotics, contain the posttranslationally modified amino acids lanthionine and methyl-lanthionine and their
precursors dehydroalanine and dehydrobutyrine [39, 81, 82]. Nisin is a pentacyclic class IA I lantibiotic consisting of 34 l-amino acids, including two
dehydroalanine residues (positions 5 and 33), a dehydrobutyrine residue
(position 2) and five intramolecular thio-ether lanthionine (residues 3–7) and
methyl-lanthionine (residues 8–11, 13–19, 23–26, 25–28) bridges (Fig. 2). Two
different forms, nisin A and nisin Z were shown to differ in only one amino acid
residue [83]. During maturation, a 23-residue leader peptide is cleaved from a
57-residue precursor molecule to result in the mature bactericidal peptide of
34 amino acid residues. Many of these lantibiotics are produced by non-lactic
acid bacteria, such as Staphylococcus, Bacillus, Streptococcus, Actinoplanes,
Streptomyces, Streptoverticillium [1, 22]. Some of them, for instance subtilin,
Pep5, and epidermin have been genetically studied in detail [29, 84–89]. The organization of the genetic determinants is comparable to that of nisin, produced
by Lactococcus lactis subsp. lactis [22, 29, 84, 86–88, 90–93].
Antimicrobial Peptides of Lactic Acid Bacteria: Mode of Action, Genetics and Biosynthesis
27
for insensitivity to the peptide antibiotic microcin 25 led to the isolation of five
categories of mutations, located in the fhuA, exb, tonB and sbmA genes [79]. The
latter three are all proteins of the cytoplasmic membrane, whereas FhuA is a
multifunctional protein of the outer membrane. [78, 79]. The region of FhuA,
which is important of microcin 25 interaction has subsequently been mapped
[80]. Several of these mutants showed an additional resistance to colicin M,
colicin B, and to bacteriophages T1 and F80 [79]. These results indicate that
microcin 25 interacts with an extracellular domain of the multifunctional
receptor FhuA, and is imported through the TonB pathway and the SbmA
protein [79].
In conclusion, pore formation in the cytoplasmic membrane seems to be a
common mode of action of those LAB bacteriocins for which the mode of
action has been determined. Some of the class II bacteriocins (lactococcin A, B,
G and lactacin F) require a specific receptor molecule for adsorption, whereas
nisin also acts on liposomes and exerts a receptor-independent action. Differences between narrow or wide host-range bacteriocins seem to be correlated
with this aspect of a specific receptor, needed for activity. However, which
bacteriocin domains confer binding specificities to lipid, protein, or reactive
groups remain to be elucidated.
3
Genetics of Bacteriocins Produced by Lactic Acid Bacteria
3.1
Nisin, the Most Prominent Member of the Class IA I Lantibiotics
The class I bacteriocins, the so-called lantibiotics, contain the posttranslationally modified amino acids lanthionine and methyl-lanthionine and their
precursors dehydroalanine and dehydrobutyrine [39, 81, 82]. Nisin is a pentacyclic class IA I lantibiotic consisting of 34 l-amino acids, including two
dehydroalanine residues (positions 5 and 33), a dehydrobutyrine residue
(position 2) and five intramolecular thio-ether lanthionine (residues 3–7) and
methyl-lanthionine (residues 8–11, 13–19, 23–26, 25–28) bridges (Fig. 2). Two
different forms, nisin A and nisin Z were shown to differ in only one amino acid
residue [83]. During maturation, a 23-residue leader peptide is cleaved from a
57-residue precursor molecule to result in the mature bactericidal peptide of
34 amino acid residues. Many of these lantibiotics are produced by non-lactic
acid bacteria, such as Staphylococcus, Bacillus, Streptococcus, Actinoplanes,
Streptomyces, Streptoverticillium [1, 22]. Some of them, for instance subtilin,
Pep5, and epidermin have been genetically studied in detail [29, 84–89]. The organization of the genetic determinants is comparable to that of nisin, produced
by Lactococcus lactis subsp. lactis [22, 29, 84, 86–88, 90–93].
Antimicrobial Peptides of Lactic Acid Bacteria: Mode of Action, Genetics and Biosynthesis
27