Natamycin is used to treat fungal infections, including Candida, Aspergillus, Cephalosporium, Fusarium, and Penicillium. It is applied topically as a cream, in eye drops, or in a lozenge. Natamycin shows negligible absorption into the body when administered in these ways. When taken orally, little or none is absorbed from the gastrointestinal tract, making it inappropriate for systemic infections. Natamycin lozenges are also prescribed to treat yeast infections and oral thrush.
Food
Natamycin has been used for decades in the food industry as a hurdle to fungal outgrowth in dairy products and other foods. Potential advantages for the usage of natamycin might include the replacement of traditional chemical preservatives, a neutral flavor impact, and less dependence on pH for efficacy, as is common with chemical preservatives. It can be applied in a variety of ways: as an aqueous suspension sprayed on the product or into which the product is dipped, or in powdered form sprinkled on or mixed into the product. While not currently approved for use on meats in the United States, some countries allow natamycin to be applied to the surface of dry and fermented sausages to prevent mold growth on the casing. Also, natamycin is approved for various dairy applications in the United States. More specifically, natamycin is commonly used in products such as cream cheeses, cottage cheese, sour cream, yogurt, shredded cheeses, cheese slices, and packaged salad mixes. One of the reasons for food producers to use natamycin is to replace the artificial preservativesorbic acid. As a food additive, it has E number E235. Throughout the European Union, it is approved only as a surface preservative for certain cheese and dried sausage products. It must not be detectable 5 mm below the rind. While natamycin is approved in different applications at different levels in the world, it is approved in over 150 countries worldwide. The European Food Safety Authority panel took over the responsibilities of providing scientific food safety advice to the EU from the Scientific Committee on Food in 2002. In 2009, the EFSA considered the proposed use levels of natamycin are safe if it is used for the surface treatment for these cheese and sausage types.
Safety
Natamycin does not have acute toxicity. In animal studies, the lowest found was 2.5-4.5 g/kg. In rats, the LD50 is ≥2300 mg/kg, and doses of 500 mg/kg/day over 2 years caused no detectable differences in survival rate, growth, or incidence of tumors. The metabolites of natamycin also lack toxicity. The breakdown products of natamycin under various storage conditions may have a lower LD50 than natamycin, but in all cases, the numbers are quite high. In humans, a dose of 500 mg/kg/day repeated over multiple days caused nausea, vomiting, and diarrhea. No evidence shows natamycin, at either pharmacological levels or levels encountered as a food additive, can harm normal intestinal flora, but definitive research may not be available. However, some people are allergic to natamycin. The EFSA has concluded that the use of natamycin as a food additive has no relevant risk for the development of resistant fungi.
Mechanism of action
Natamycin inhibits the growth of fungi by specifically binding to ergosterol present in fungal cell membranes. The molecule interacts irreversibly with the sterol forming a sandwich-like structure embedded in the hydrophobic core of the membrane; between the two lipid layers. This causes membrane fragmentation and indirectly affects the functions ergosterol takes part in, such as endocytosis and exocytosis, vacuole fusion, morphogenesis, and amino acid and glucose transport across the membrane. Natamycin has very low solubility in water; however, natamycin is effective at very low levels. Its minimum inhibitory concentration is less than 10 ppm for most molds.
History
It is produced as a secondary metabolite by some Streptomyces species: S. natalensis, S. lydicus, S. chattanoogensis and S. gilvosporeus. Natamycin was first isolated in 1955 from fermentation broth of a Streptomyces natalensis cell culture.. It was originally named pimaricin to honor Pietermaritzburg, where Streptomyces natalensis was acquired. Pimaricin was later renamed natamycin after the World Health Organization mandated that antibiotics produced by Streptomyces end in –mycin. The name also related to the organism producing the compound, Streptomyces natalensis, hence the name natamycin.
Society and culture
Natamycin appears on Whole Foods' “Unacceptable Ingredients for Food” list.
