Nisin is an antibacterial peptide produced by Lactococcus
lactis subsp. lactis that exhibits a broad spectrum of inhibitory
activity against gram-positive organisms including bacterial
spores. In a recent international patent application by
Blackburn et al. (2), it was reported that nisin used in
combination with a chelating agent exhibited a bactericidal
effect towards both gram-positive and gram-negative bacteria.
Kordel and Sahl (5) showed that Escherichia coli exhibited
nisin sensitivity when the outer membrane could be
altered by treatments such as osmotic shock. In the United
States, nisin has received GRAS (generally recognized as
safe) status and is approved for use in some processed
cheese spreads to prevent the outgrowth of clostridial spores
and toxin production. In addition, nisin has been used to
inactivate thermophilic spoilage organisms in canned goods
and to extend the shelf life of milk and dairy products (3).
The bactericidal action of nisin occurs in the cytoplasmic
membrane of vegetative cells (6). Cellular damage can range
from the loss of the proton motive force to the disruption of
the cellular integrity of the membrane. Recently, Liu and
Hansen (7) demonstrated that the dehydroalanine and dehydrobutyrine
residues in active nisin play a direct role by
acting as electrophilic Michael acceptors toward nucleophiles
in the cytoplasmic membrane.
The outer membrane of gram-negative bacteria acts as a
permeability barrier for the cell. It is responsible for preventing
molecules such as antibiotics, detergents, and dyes from
reaching the cytoplasmic membrane (8). Gram-negative bacteria
are not generally sensitive to nisin (4, 9). Although the
cytoplasmic membrane should be susceptible, the outer
membrane protects the cell by excluding nisin (6). Magnesium
ions serve to stabilize the lipopolysaccharide layer of
the outer membrane. Chelating agents, such as EDTA, bind