Lantibiotic nisin-Z

Nisin Z is a possible alternative for treating bovine mastitis by inhibiting mastitis-causing pathogens and having anti-inflammatory activity. However, the anti-inflammatory mechanism of nisin Z on mastitis is unknown. Our study aimed to investigate the mechanisms of nisin Z on mastitis. Our results showed that nisin Z inhibited the activation of the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathway, decreased the release of pro-inflammatory cytokines (i.e., tumor necrosis factor-α, IL-1β, and IL-6), and increased the anti-inflammatory cytokine (IL-10) in lipopolysaccharide (LPS)-induced MCF10A cells. After intraperitoneal injection, nisin Z significantly decreased inflammatory cell infiltration in the mammary gland, as well as decreased myeloperoxidase and pro-inflammatory cytokines in serum and mammary gland. Western blot analysis revealed that nisin Z also dramatically suppressed the activation of the ERK1/2 and p38 MAPK signaling pathways in LPS-induced mastitis mice. We also found that nisin Z treatment could enhance the blood-milk barrier. In summary, our study demonstrated that nisin Z exerted an anti-inflammatory effect by inhibiting the ERK1/2 and p38 MAPK signaling pathway and promoting the blood-milk barrier on LPS-induced mastitis.

The lantibiotic nisin, usually used as a 2.5%w/w in NaCl and milk solids, has activity against a wide range of Gram-positive bacteria, especially food-borne pathogens, and has been used as a food preservative for decades without the development of significant resistance. It has been reported that the high purity (>95%) nisin Z form has activity against the Gram-negative speciesE. coli, which is significantly reduced in the presence of NaCl. This current study examined, by1H NMR spectroscopy, the effects of NaCl, and a range of other salts, on the observed aqueous solution1H NMR spectra of nisin Z in the pH 3-4 range, where nisin Z has its maximum stability. Nisin's mechanism of action involves binding to the polyoxygenated pyrophosphate moiety of lipid II, and in acidic solution the positively charged C-terminus region is reported to interact with the negative sulfate groups of SDS micelles, so the study was extended to include a number of polyoxygenated anions commonly used as buffers in many biological assays. In general, the biggest changes found were in the chemical shifts of protons in the hydrophobic N-terminus region, rather than the more polar C-terminus region. The effects seen on the addition of the salts (cations and anions) were not just an overall non-specific ionic strength effect, as different salts caused different effects, in an unpredictive manner. Similarly, the polyoxygenated anions behaved differently and not predictably, and neither the cations/anions, or polyoxygenated anions, constitute a Hofmeister or inverse Hofmeister series.

Lactococcus lactis strain NIZO 22186 produces an extracellular, lanthionine-containing 3.5-kDa polypeptide with antimicrobial activity. Its retention time on reversed-phase (RP) HPLC and its amino acid composition showed high similarities but no complete identity to nisin. The gene for this lantibiotic, designated nisZ, has been cloned and its nucleotide sequence was found to be identical to that of the precursor nisin gene apart from a single mutation resulting in the substitution His27Asn in the mature polypeptide. NMR studies of the natural nisin variant, which has been designated nisin Z, confirmed the His27Asn substitution and indicated that it has a similar structure to nisin.