A Powerful Inhibitory Substance Produced by Group N Streptococci

Mattick, A. T. R.; Hirsch, A.

doi:10.1038/154551a0

Cited by 121 publications

(58 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Whereas the wedge model may illustrate results obtained with model membranes, a number of effects observed with intact living cells remain unexplained; in particular, the fact that nisin acts on model membranes at micromolar concentrations whereas in vivo minimal inhibitory concentration (MIC) 1 values are in the nanomolar range. The discrepancies were explained by the finding that nisin and epidermin use lipid II, the bactoprenol-bound precursor of the bacterial cell wall as a docking molecule for subsequent pore formation (12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Specific Binding of Nisin to the Peptidoglycan Precursor Lipid II Combines Pore Formation and Inhibition of Cell Wall Biosynthesis for Potent Antibiotic Activity

Wiedemann¹,

Breukink²,

Kraaij³

et al. 2001

Journal of Biological Chemistry

676

609

View full text Add to dashboard Cite

؊1 for the wildtype peptide, and the minimum concentration for pore formation increased from the 1 nM to the 50 nM range. In contrast, peptides mutated in the flexible hinge region, e.g. [⌬N20/⌬M21]nisin, were completely inactive in the pore formation assay, but were reduced to some extent in their in vivo activity. We found the remaining in vivo activity to result from the unaltered capacity of the mutated peptide to bind to lipid II and thus to inhibit its incorporation into the peptidoglycan network. Therefore, through interaction with the membrane-bound cell wall precursor lipid II, nisin inhibits peptidoglycan synthesis and forms highly specific pores. The combination of two killing mechanisms in one molecule potentiates antibiotic activity and results in nanomolar MIC values, a strategy that may well be worth considering for the construction of novel antibiotics.The antimicrobial peptide nisin is produced by numerous strains of Lactococcus lactis and inhibits a broad range of Gram-positive bacteria (1, 2). It belongs to the lantibiotics, a group of antimicrobial peptides that is characterized by the presence of intramolecular rings formed by the thioether amino acids lanthionine and 3-methyllanthionine (3, 4). Nisin has had a long history as a potent and safe food preservative, although recent insight into the molecular mechanism of its bactericidal activity also make it interesting for biomedical applications (5, 6). Generally, the nisin-type subgroup of lantibiotics comprises elongated cationic peptides that have the capacity to adopt amphiphilic structures. Such peptides are assumed to kill microbes by disturbing the integrity of the energy-transducing membrane. Indeed, early experiments demonstrated that nisin or related lantibiotics induced rapid efflux of ions or cytoplasmic solutes such as amino acids and nucleotides. The concomitant depolarization of the cytoplasmic membrane resulted in an instant termination of all biosynthetic processes (7,8). Structural analysis in the presence of micelles indicated that the hydrophilic groups of the peptide interact with the phospholipid headgroups, and the hydrophobic side chains are immersed in the hydrophobic core of the membrane (9, 10). The wedge model as proposed by Driessen et al. (11) takes into account such structural data and proposes that the peptides insert into the membrane without losing contact with the membrane surface, resulting in the formation of a short-lived pore.Whereas the wedge model may illustrate results obtained with model membranes, a number of effects observed with intact living cells remain unexplained; in particular, the fact that nisin acts on model membranes at micromolar concentrations whereas in vivo minimal inhibitory concentration (MIC) 1 values are in the nanomolar range. The discrepancies were explained by the finding that nisin and epidermin use lipid II, the bactoprenol-bound precursor of the bacterial cell wall as a docking molecule for subsequent pore formation (12). The specificity of the nisin-lipid II interaction a...

show abstract

mentioning

confidence: 99%

“…The antimicrobial peptide nisin is produced by numerous strains of Lactococcus lactis and inhibits a broad range of Gram-positive bacteria (1,2). It belongs to the lantibiotics, a group of antimicrobial peptides that is characterized by the presence of intramolecular rings formed by the thioether amino acids lanthionine and 3-methyllanthionine (3,4).…”

mentioning

confidence: 99%

Specific Binding of Nisin to the Peptidoglycan Precursor Lipid II Combines Pore Formation and Inhibition of Cell Wall Biosynthesis for Potent Antibiotic Activity

Wiedemann¹,

Breukink²,

Kraaij³

et al. 2001

Journal of Biological Chemistry

676

609

View full text Add to dashboard Cite

show abstract

“…The assay of nisin has presented difficulties and a number of methods have been proposed (Mattick and Hirsch, 1947;Hirsch, 1950;Friedmann and Epstein, 1951;Friedmann and Beach, 1951).…”

Section: Some Properties Of Nisin Experimentalmentioning

confidence: 99%

“…There are so many effective ways of dealing with infections by Str. pyogenes that the undoubted great protective effects of nisin in mice infected with this organism, in which the results of Mattick and Hirsch (1947) are confirmed, will probably never lead to a trial against natural infection in man.…”

mentioning

confidence: 99%

Some Properties of Nisin

Gowans

Smith

Florey

1952

British Journal of Pharmacology and Chemotherapy

View full text Add to dashboard Cite

show abstract

“…The protein was concentrated and tested against pathogenic streptococci (Mattick and Hirsch, 1944) and later the same protein that was inhibitory was used to treat bovine mastitis (Taylor et al, 1949). Similarly, intersection studies showed that a Staphylococcus isolate could inhibit Corynebacterium diphtheriae.…”

Section: Introductionmentioning

confidence: 99%

Microbial defense systems in foods and feeds

Fatima¹

2017

JBC

View full text Add to dashboard Cite

Bacteriocins are proteinaceous substances having antigenic and developed by some microbial strains having the ability and effectiveness against pathogenic bacteria and spoilage, harmless to the consumer, and have no adverse effect on the organoleptic product quality. Bacteriocins are rendered inactive by the action of proteolytic enzymes present in the gastrointestinal tract, thy can resist high temperatures, are non-toxic and does not compromise the immune system in experimental animals. Bacteriocins as microbial defense systems has been widely researched and documented. However, though the diversity and abundance of bactrocins is very high, indicating their use as microbial weapons, research on ecological and evolutionary significance needs elaborate studies. More advanced studies are needed to unfold reasons for their success as toxins.

show abstract

A Powerful Inhibitory Substance Produced by Group N Streptococci

Cited by 121 publications

References 3 publications

Specific Binding of Nisin to the Peptidoglycan Precursor Lipid II Combines Pore Formation and Inhibition of Cell Wall Biosynthesis for Potent Antibiotic Activity

Specific Binding of Nisin to the Peptidoglycan Precursor Lipid II Combines Pore Formation and Inhibition of Cell Wall Biosynthesis for Potent Antibiotic Activity

Some Properties of Nisin

Microbial defense systems in foods and feeds

Contact Info

Product

Resources

About