Nisin is a polycyclic antibacterial

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

produced by the

bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were amon ...

Lactococcus lactis ''Lactococcus lactis'' is a Gram-positive bacterium used extensively in the production of buttermilk and cheese, but has also become famous as the first genetically modified organism to be used alive for the treatment of human disease. ''L. lact ...

'' that is used as a food

preservative A preservative is a substance or a chemical that is added to products such as food products, beverages, pharmaceutical drugs, paints, biological samples, cosmetics, wood, and many other products to prevent decomposition by microbial growth or by ...

. It has 34

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

residues, including the uncommon amino acids

lanthionine Lanthionine is a nonproteinogenic amino acid with the chemical formula (HOOC-CH(NH2)-CH2-S-CH2-CH(NH2)-COOH). It is typically formed by a cysteine residue and a dehydrated serine residue. Despite its name, lanthionine does not contain the element ...

(Lan), methyllanthionine (MeLan),

didehydroalanine Dehydroalanine (Cα,β-didehydroalanine, α,β-di-dehydroalanine, 2-aminoacrylate, or 2,3-didehydroalanine) is a dehydroamino acid. It does not exist in its free form, but it occurs naturally as a residue found in peptides of microbial origin. A ...

(Dha), and didehydroaminobutyric acid (Dhb). These unusual amino acids are introduced by

posttranslational modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribo ...

of the precursor peptide. In these reactions a ribosomally synthesized 57-mer is converted to the final peptide. The unsaturated amino acids originate from serine and threonine, and the enzyme-catalysed addition of cysteine residues to the didehydro amino acids result in the multiple (5)

thioether In organic chemistry, an organic sulfide (British English sulphide) or thioether is an organosulfur functional group with the connectivity as shown on right. Like many other sulfur-containing compounds, volatile sulfides have foul odors. A su ...

bridges. Subtilin and epidermin are related to nisin. All are members of a class of molecules known as

lantibiotics Lantibiotics are a class of polycyclic peptide antibiotics that contain the characteristic thioether amino acids lanthionine or methyllanthionine, as well as the Saturated and unsaturated compounds, unsaturated amino acids dehydroalanine, and 2-Am ...

. In the food industry, nisin is obtained from the culturing of ''L. lactis'' on natural substrates, such as milk or dextrose, and it is not chemically synthesized. It was originally isolated in the late 1930s, and produced since the 1950s as Nisaplin from naturally occurring sources by Aplin and Barrett in laboratories in

Beaminster Beaminster ( ) is a town and civil parish in Dorset, England, situated in the Dorset Council administrative area approximately northwest of the county town Dorchester. It is sited in a bowl-shaped valley near the source of the small River ...

in Dorset (now owned by DuPont), and approved as an additive for food use in the US in the late 1960s.

Properties

While in general most

bacteriocins Bacteriocins are proteinaceous or peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are similar to yeast and paramecium killing factors, and are structurally, functionally, and ec ...

inhibit only closely related species, nisin is a rare example of a "broad-spectrum" bacteriocin effective against many

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

organisms, including

lactic acid bacteria Lactobacillales are an order of gram-positive, low-GC, acid-tolerant, generally nonsporulating, nonrespiring, either rod-shaped ( bacilli) or spherical ( cocci) bacteria that share common metabolic and physiological characteristics. These bact ...

(commonly associated to avoid food spoilage),''

Listeria monocytogenes ''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host ...

'' (a known pathogen), '' Staphylococcus aureus'', ''

Bacillus cereus ''Bacillus cereus'' is a Gram-positive rod-shaped bacterium commonly found in soil, food, and marine sponges. The specific name, ''cereus'', meaning "waxy" in Latin, refers to the appearance of colonies grown on blood agar. Some strains are har ...

'', ''

Clostridium botulinum ''Clostridium botulinum'' is a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum. The botulinum toxin can cause botulism, a severe flaccid paralytic disease in humans ...

'', etc. It is also particularly effective against spores.

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...

bacteria are protected by their outer membrane but may become susceptible to nisin action after a heat shock or when this is coupled with the chelator

EDTA Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes ev ...

. When used in combination with EDTA, nisin has the ability to inhibit '' E. coli O157:H7'' and ''

Salmonella enterica ''Salmonella enterica'' (formerly ''Salmonella choleraesuis'') is a rod-headed, flagellate, facultative anaerobic, Gram-negative bacterium and a species of the genus ''Salmonella''. A number of its serovars are serious human pathogens. Epidemi ...

''. Nisin, as a class I bacteriocin, is very stable at acidic pHs and is more heat stable at lower pHs. The mode of action of Nisin against pathogens such as ''L. monocytogenes'' is to dissipate the membrane potential and pH gradient. Nisin is soluble in water and can be effective at levels nearing the parts-per-billion range. Nisin concentration can be measured using various techniques such as

chromatography In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system ( ...

or by a simple agar diffusion bioassay.

Applications

Food production

Nisin is used in processed cheese, meats, beverages, etc. during production to extend shelf life by suppressing Gram-positive spoilage and pathogenic bacteria. In foods, it is common to use nisin at levels ranging from ~1-25 ppm, depending on the food type and regulatory approval. As a food additive, nisin has an E number of E234.

Other

Due to its naturally selective spectrum of activity, it is also employed as a selective agent in microbiological media for the isolation of gram-negative bacteria, yeast, and moulds. Nisin has also been used in food packaging applications and can serve as a preservative by controlled release onto the food surface from the polymer packaging. In combination with

miconazole Miconazole, sold under the brand name Monistat among others, is an antifungal medication used to treat ring worm, pityriasis versicolor, and yeast infections of the skin or vagina. It is used for ring worm of the body, groin (jock itch), and ...

it has been studied as a possible treatment for infections of '' Clostridium difficile''.

References

External links