Nisin

Abstract

Following its discovery in the late 1920s, the bacteriocin nisin has now been in use as a food preservative for almost 50 years (McLintock et al., 1952). Nisin is a low-molecular-weight polypeptide produced by the bacterial dairy starter culture Lactococcus lactis subspecies lactis. It has a much broader spectrum than most other bacteriocins, being active against a wide range of Grampositive bacteria. Since this group of organisms includes heat-resistant bacteria, nisin has become a widely used food preservative because it can maintain or even extend the shelf life of heat-treated foods and contribute to their safety. The characterization of the molecule was first conducted by Mattick and Hirsch (1947), who coined its name from the term “N inhibitory substance.” At that time, the producer organism was classified as Lancefield serologic group N Streptococcus. When its potential as a food preservative was realized (Hirsch et al., 1951), the first commercial extract of nisin was developed by Aplin & Barrett Ltd. (now part of Danisco) in 1957. Nisin has been studied by many research groups, both academic and industrial, because of its many positive attributes - broad-spectrum antimicrobial activity, long history of successful usage as a food preservative, excellent safety record - and its designation as a natural food additive. Nisaplin (which was nisin A) is the first commercial extract of nisin, developed between 1962 and 1965. Apart from numerous research papers on nisin, several reviews have been published, most notably those by Hurst (1981,1983), Delves-Broughton (1990), Ray (1992), Hurst and Hoover (1993), de Vuyst and Vandamme (1994), Delves-Broughton and Gasson (1994), Delves-Broughton et al. (1996), Thomas et al. (2000), and Thomas and Delves-Broughton (2001). Toxicity testing results demonstrating its safety for human consumption were published in 1962 (Frazer et al., 1962; Hara et al. 1962). Nisin was approved for use in food in 1969 by the Joint Food and Agriculture Organization/World Health Organization (FAO/WHO) Committee on Food Additives and was awarded generally recognized as safe (GRAS) status in the United States in 1988 (FDA, 1988). It remains the only bacteriocin allowed in food as an added preservative. Food safety is a major concern internationally. Increasing mass production and the longer distribution chains operating in many countries have led to an increase in foodborne illnesses with associated fatalities. Consumers do not want high levels of chemical food preservatives in their food and yet they increasingly look for convenient, long-life food that is of high quality but that is not severely processed (Gould, 1992). Nisin represents a safe, natural method of preservation that can be used as part of a combined preservative system to increase the safety and shelf life of food. Nisin-producing lactococci occur naturally in milk; consequently nisin can be present naturally at low levels in both soured milk and cheese. One of the earliest reports about “inhibitory streptococci” concerned milk in which cheese starter organisms failed to develop (Whitehead and Riddet, 1933). Nisin was also shown to be present in farmhouse cheese (Chevalier et al., 1957). Therefore, it is likely that nisin or substances similar to it have been consumed for a significant length of time without apparent ill effects. There has been misplaced concern expressed in some quarters resulting from a confusion arising from references to nisin as an antibiotic (Hansen, 1993; Hurst, 1981). Although there is no doubt that therapeutic drugs associated with medical usage should not be used in food applications, nisin is not one of these agents. There are clear differences between this bacteriocin and pharmaceutical antibiotics (Cleveland and Tchikindas, 2001). Before its development as a food preservative, there were attempts to use nisin as a medical drug, but these attempts failed because of nisin’s lack of activity against Gram-negative bacteria and its rapid digestion and breakdown within the body. Generally antibiotics are secondary metabolites. Nisin is a primary metabolite produced by a process involving ribosomal transcription and translation. Nisin is not used therapeutically in human or veterinary medicine nor is it used as an animal feed additive or for growth promotion. Various studies have shown that nisin will not contribute to antibiotic drug resistance. For instance, passaging of bacteria in media containing sublethal concentrations of nisin did not alter the sensitivity of the test organisms to therapeutic antibiotics and other chemotherapeutic drugs (Hossack et al., 1983). We recommend that nisin (and other bacteriocins) should be considered as antimicrobial peptides and not referred to as antibiotics. Regulatory authorities and food producers acknowledge and appreciate that nisin does not hide poor manufacturing practice. Nisin is not effective against Gram-negative bacteria, yeasts, and molds, or microorganisms that should be killed by normal pasteurization treatments and that are only present in such foods if the heat treatment is inadequate or if postprocessing contamination has occurred. The effectiveness of nisin is also dependent on the bacterial load (Scott and Taylor, 1981b). Nisin will be less effective in a processed food that has a high spore count; this would usually be the result of poor-quality ingredients (Gibbs and Hurst, 1964). Apart from the advantages already mentioned, nisin offers the possibility (within safety limits) of energy saving and consequent cost cutting. Thermally injured spores are more sensitive to nisin, and extended shelf life can be achieved with a combination of nisin and a reduced heat treatment.