Peptide Antibiotic Nisin Research Articles

Voltage-dependent depolarization of bacterial membranes and artificial lipid bilayers by the peptide antibiotic nisin.

The peptide antibiotic nisin is shown to disrupt valinomycin-induced potassium diffusion potentials imposed on intact cells of Staphylococcus cohnii 22. Membrane depolarization occurred rapidly at high diffusion potentials while at low potentials nisin-induced depolarization was slower suggesting that nisin requires a membrane potential for activity. This assumption was proven in experiments with planar lipid bilayers (black lipid membranes). Macroscopic conductivity measurements indicated a voltage-dependent action of nisin. The potential must have a trans-negative orientation with respect to the addition of nisin (added to the cis-side) and a sufficient magnitude (ca.-100 mV). With intact cells the threshold potential was lower (-50 to -80 mV at pH 7.5 and below -50 mV at pH 5.5). Single channel recordings resolved transient multi-state pores, strongly resembling those introduced by melittin into artificial bilayers. The pores had diameters in the range of 0.2-1 nm, and lifetimes of few to several hundred milliseconds. The results indicate that nisin has to be regarded as a membrane-depolarizing agent which acts in a voltage-dependent fashion.

Synthetic Study on Peptide Antibiotic Nisin. II. The Synthesis of Ring B

Abstract Synthesis of a cyclic sulfide moiety ring B in peptide antibiotic nisin was successfully achieved by desulfurization from a corresponding disulfide peptide with tris(diethylamino)phosphine. The configuration on β-carbon atom of threo-3-methyl-d-cysteineresidue in the disulfide peptide was retained through the reaction to give a desired natural threo form of methyllanthionine.

Mode of action of the peptide antibiotic nisin and influence on the membrane potential of whole cells and on cytoplasmic and artificial membrane vesicles.

The peptide antibiotic nisin was shown to cause a rapid efflux of amino acids and Rb+ from the cytoplasm of gram-positive bacteria (Staphylococcus cohnii 22, Bacillus subtilis W 23, Micrococcus luteus ATCC 4698, and Streptococcus zymogenes 24). It strongly decreased the membrane potential of cells as judged by the distribution of the lipophilic tetraphenylphosphonium cation. Ascorbate-phenazine methosulfate-driven transport of L-proline by cytoplasmic membrane vesicles was blocked after addition of nisin, and accumulated amino acids were released from the vesicles. Soybean phospholipid (asolectin) vesicles were not affected by nisin. The data suggest that the cytoplasmic membrane is the primary target and that membrane disruption accounts for the bactericidal action of nisin.

Structural similarities of the staphylococcin-like peptide Pep-5 to the peptide antibiotic nisin.

The staphylococcin-like peptide Pep-5 was shown to be a complex mixture of closely related and strongly basic peptides. Five peptides were purified by high-pressure liquid chromatography on reversed-phase and gel filtration columns and further characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino acid analysis. Four peptides have molecular weights of ca. 3,500, whereas one is of double size. All contain the thioether amino acid lanthionine and a large number of lysine residues per molecule. The amino terminus of the main active peptide is blocked; the carboxy-terminal end is formed by a lysine residue. The data obtained for Pep-5 suggest striking structural similarities to the peptide antibiotics nisin and subtilin.

Synthetic Study on Peptide Antibiotic Nisin. I. The Synthesis of Ring A

Abstract Synthesis of the ring A, a cyclic sulfide peptide part containing dehydroalanine residue, in peptide antibiotic nisin was successfully achieved by applications of two novel procedures. First, a sulfide ring was derived from a cyclic disulfide peptide by desulfurization with P(Et2N)3. Secondly, for the preparation of dehydroalanyl residue, a simple and convenient method through Hofmann degradation of 2,3-diaminopropionyl residue was newly exploited in the presence of sulfide linkage.

ChemInform Abstract: SYNTHESIS OF THREO‐3‐METHYLCYSTEINE FROM THREONINE

AbstractDie Titelverbindung (VI) als Bestandteil von β‐Methyllanthionin (VII) im Peptidantibioticum Nisin wird in ihrer oxidierten Form (V) ausgehend vom Aziridin (I) [zugänglich aus D‐Threonin] über die Stufen (IIIa)+(IIIb) (trennbares Gemisch) und (IV) synthetisiert.

Synthesis of threo-3-Methylcysteine from Threonine

Abstract threo-3-Methyl-d-cysteine as a moiety of β-methyllanthionine in the peptide antibiotic nisin was synthesized stereospecifically. The reaction of (2R,3R)-3-methyl-2-aziridinecarboxylic acid derivative prepared from d-threonine with thiobenzoic acid gave the β-mercapto α-amino acid derivative of the same configuration as the starting material. A stereochemistry of the product was retained as a result of double inversion mechanism through the reactions. Thus, we could prepare threo-3-methyl-d-cysteine, i.e., (2S,3S)-2-amino-3-mercaptobutanoic acid which is required for the synthetic study of nisin.

NIH chemists determine primary structure of peptide antibiotic nisin

NIH chemists determine primary structure of peptide antibiotic nisin

Lantibiotics: A Candidate for Future Generation of Antibiotics

Emergence of multi-resistant pathogens has urged the exploration of antibiotic repertoires. The long reliability on the glycopeptide antibiotic vancomycin against fatal diseases caused by Gram-positive bacteria is also in wrecked to insist on finding more promising alternative antibiotics. The peptide antibiotic nisin is effective against vancomycin resistant bacteria. Nisin is the first lantibiotic that was discovered before penicillin and has been widely used as a safe alternative for chemical reagents in food preservation in around 50 countries for over 40 years without natural resistance development. Therefore, lantibiotics are one of the most promising alternative candidate for future antibiotics that maintain their antibacterial efficacy by many modes of action. Till now, more than 60 lantibiotics have been isolated, identified and characterized. We explained various aspects of biosynthesis, grouping, mutagenesis, activities and modes of action of lantibiotics in this review. DOI: http://dx.doi.org/10.3329/sjm.v1i1.9096 Stamford Journal of Microbiology, Vol.1(1), July 2011, p.1-12