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Mechanism of lantibiotic-induced pore-formation

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Abstract

Nisin and other lantibiotics have a bacteriocidal effect against Gram-positive bacteria, and also inhibit the outgrowth of bacterial spores. The bacteriocidal effect appears to be due to the formation of pores in the bacterial membrane. In the absence of anionic membrane phospholipids, the lantibiotic nisin acts as an anion selective carrier. In the presence of anionic phospholipids, nisin forms nonselective, transient, multi-state pores in cells, proteoliposomes, liposomes and black lipid membranes. Pore formation involves distinct steps. First, nisin associates tightly with the anionic membrane surface leading to a high local concentration. This results in a disturbance of the lipid dynamics near the phospholipid polar head group-water interface, and an immobilization of lipids. In the presence of a transmembrane electrical potential above the threshold level, the molecules reorient, presumably as an aggregate, from a surface-bound into a membrane-inserted configuration. Co-insertion of bound, anionic phospholipids results in bending of the lipid surface giving rise to a wedge-like, nonspecific, water-filled pore.

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Abbreviations

Δψ:

transmembrane electrical potential

Δp:

proton motive force

References

  • Abee T, Gao FH & Konings WN (1991) The mechanism of action of the lantibiotic nisin in artificial membranes. In: Jung G & Sahl H-G (Eds) Nisin and novel lantibiotics (pp 373–386). Escom, Leiden

    Google Scholar 

  • Benz R, Jung G & Sahl H-G (1991) Mechanism of channel formation by lantibiotics in black lipid membranes. In: Jung G & Sahl H-G (Eds) Nisin and novel lantibiotics (pp 359–372). Escom, Leiden

    Google Scholar 

  • Bierman G & Sahl H-G (1985) Induction of autolysis of Staphylococci by the basic peptide antibiotics Pep5 and nisin and their influence on the activity of autolytic enzymes. Arch. Microbiol. Lett. 58: 223–228

    Google Scholar 

  • Bierman G & Sahl H-G (1987) Autolytic system of Staphylococcus simulans 22: influence of cationic peptides on activity of N-acetylmuramoyl-L-alanine amidase. J. Bact. 169: 5452–5458

    PubMed  Google Scholar 

  • Bierman G & Sahl H-G (1988) Influence of cationic peptides on the activity of the autolytic endo-β-N-acetylglucosamidase of Staphylococcus simulans 22. FEMS Microbiol. Lett. 58: 223–228

    Google Scholar 

  • Bierman G & Sahl H-G (1991) Induction of autolysis of Staphylococcus simulans 22 by Pep5 and nisin and influence of the cationic peptides on the activity of the autolytic enzymes. In: Jung G & Sahl H-G (Eds) Nisin and novel lantibiotics (pp 386–396). Escom, Leiden

    Google Scholar 

  • Bruno MEC, Kaiser A & Montville TJ (1992) Depletion of proton motive force by nisin in Listera monocytogenes cells. Appl. Environ. Microbiol. 58: 2255–2259

    PubMed  Google Scholar 

  • Chan WC, Bycroft BW, Lian LY & Roberts GCK (1989) Isolation and characterisation of two degradation products derived from the peptide antibiotic nisin. FEBS Lett. 252: 29–36

    Article  Google Scholar 

  • Chan WC, Roberts GCK & Bycroft BW (1993) Structure-activity relationships of nisin and subtilin. In: Schneider CH & Eberle AN (Eds) Peptides 1992 (pp 770–771). Escom Science Publishers, Leiden

    Google Scholar 

  • Chan WC, Dodd HM, Maclean K, Lian LY, Bycroft BW, Gassen MJ & Roberts, GCK (1995a) Structure-activity relationships in the peptide antibiotic nisin: the role of dehydroalanine 5. Molec. Microbiol. (submitted)

  • Chan WC, Leyland M, Clarke J, Lian LY, Gassen MJ, Bycroft BW & Roberts, GCK (1995b) Structure-activity relationships in the peptide antibiotic nisin: biological activity of proteolytic fragments of the molecule. (in prep)

  • Demange P, Voges D, Benz J, Liemann S, Göttig P, Berendes R, Burger A & Huber R (1994) Annexin V: the key to understanding ion selectivity and voltage regulation. Trends. Biochem. Sci. 19: 272–276

    Article  PubMed  Google Scholar 

  • Driessen AJM, van denHooven HW, Kuiper W, van deKamp M, Sahl H-G, Konings RNH & Konings WN (1995) Mechanistic studies of lantibiotic-induced permeabilization of phospholipid vesicles. Biochemistry 34: 1606–1614

    PubMed  Google Scholar 

  • Gao FH, Abee T & Konings WN (1991) Mechanism of action of the peptide antibiotic nisin in liposomes and cytochrome c oxidase-containing proteoliposomes. Appl. Environ. Microbiol. 57: 2164–2170

    PubMed  Google Scholar 

  • García Garcerá MJ, Elferink MGL, Driessen AJM & Konings WN (1993) In vitro pore-forming activity of the lantibiotic nisin. Eur. J. Biochem. 212: 417–422

    PubMed  Google Scholar 

  • Gross E & Morell JL (1971) The presence of dehydroalanine in the antibiotic nisin and its relationship to activity. J. Am. Chem. Soc. 93: 4634–4635

    PubMed  Google Scholar 

  • Jung G (1991) Lantibiotics: a survey. In: Jung G & Sahl H-G (Eds) Nisin and novel lantibiotics (pp 1–30). Escom, Leiden

    Google Scholar 

  • Klaenhammer TR (1993) Genetics of bacteriocins produced by lactic acid bacteria. FEMS Microbiol. Rev. 12: 39–86

    Article  PubMed  Google Scholar 

  • Kordel M & Sahl H-G (1986) Susceptibility of bacterial eukaryotic and artificial membranes to the disruptive action of the cationic peptides Pep5 and nisin. FEMS Microbiol. Lett. 34: 139–144

    Article  Google Scholar 

  • Lian LY, Chan WC, Morley SD, Roberts GCK, Bycroft BW & Jackson D. (1991) NMR studies of the solution structure of nisin A and related peptides. In: Jung G & Sahl HG (Eds) Nisin and novel lantibiotics (pp 43–58). Escom Science Publishers, Leiden

    Google Scholar 

  • Lian LY, Chan WC, Morley SD, Roberts GCK, Bycroft BW and Jackson D (1992) Solution structures of nisin A and its two major degradation products determined by NMR. Biochem. J. 283: 413–420

    PubMed  Google Scholar 

  • Liu W & Hansen JN (1990) Some chemical and physical properties of nisin, a small protein antibiotic produced by Lactococcis lactis. Appl. Environ. Microbiol. 56: 2551–2558

    PubMed  Google Scholar 

  • Liu W & Hansen JN (1993) The antimicrobial effect of a structural variant of subtilin against outgrowing Bacillus cereus T spores and vegetative cells occurs by different mechanisms. Appl. Environm. Microbiol. 59: 648–651

    Google Scholar 

  • Morris SL, Walsh RC & Hansen JN (1984) Identification and characterization of some bacterial membrane sulfhydryl groups which are targets of bacteriostatic and antibiotic action. J. Biol. Chem. 259: 13590–13594

    PubMed  Google Scholar 

  • Okereke A & Montville TJ (1992) Nisin dissipates the proton motive force of the obligate anaerobe Clostridium sporogenes PA 3679. Appl. Environ. Microbiol. 58: 2463–2467

    PubMed  Google Scholar 

  • Reisinger P, Seidel H, Tschesche H and Hammes WP (1980) The effect of nisin on murein synthesis. Archiv. Microbiol. 127: 187–193

    Google Scholar 

  • Ruhr E & Sahl H-G (1985) Mode of action of the peptide antibiotic nisin and influence on the membrane potential of whole cells and on cytoplasmic and artificial membrane vesicles. Antimicrob. Agents Chemother. 27: 841–845

    PubMed  Google Scholar 

  • Sahl H-G and Brandis H (1981) Production, purification and chemical properties of an antistaphylococcal agent produced by Staphylococcus epidermis. J. Gen. Microbiol. 127: 377–383

    PubMed  Google Scholar 

  • Sahl H-G, Großgarten M, Widger WR, Cramer WA and Brandis H (1985) Structural similarities of the Staphylococcin-like peptide Pep-5 to the peptide antibiotic nisin. Antimicrobial Agents and Chemother. 27: 836–840

    Google Scholar 

  • Sahl H-G, Kordel M & Benz R (1987) Voltage dependent depolarization of bacterial membranes and artificial lipid bilayers by the peptide antibiotic nisin. Arch. Microbiol. 149: 120–124

    PubMed  Google Scholar 

  • Sahl H-G (1991) Pore formation in bacterial membranes by cationic lantibiotics. In: Jung G & Sahl H-G (Eds) Nisin and novel lantibiotics (pp 347–358). Escom, Leiden

    Google Scholar 

  • Sahl H-G, Jack, RW & Bierbaum G (1995) Lantibiotics: biosynthesis and biological activities of peptides with unique post-translational modifications. Eur. J. Biochem. in press.

  • Stevens KA, Sheldon BW, Klapes NA & Klaenhammer TR (1991) Nisin treatment for inactivation of Salmonella species and other Gram-negative bacteria. Appl. Environ. Microbiol. 57: 3613–3615

    PubMed  Google Scholar 

  • Van denHooven HW, Fogolari F, Rollema HS, Konings RNH, Hilbers CW & van deVen FJM (1993) NMR and circular dichroism studies of the lantibiotic nisin in non aqueous environments. FEBS Lett. 319: 189–194

    Article  PubMed  Google Scholar 

  • Van deKamp M, Horstink LM, van denHooven HW, Konings RNH, Hilbers CW, Frey A, Sahl H-G, Metzger JW, Jung G, & van deVen FJM (1995) Sequence analysis by NMR spectroscopy of the peptide lantibiotic epilancin K7 from Staphylococcus epidermis K7. Eur. J. Biochem. 227: 757–771

    PubMed  Google Scholar 

  • Van deVen FJM, van denHooven HW, Konings RNH & Hilbers CW (1991) NMR and circular dichroism studies of the lantibiotic nisin in non aqueous environments. Eur. J. Biochem. 202: 1181–1188

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology, University of Groningen, Kerlaan 30, 9751 NN, Haren, the Netherlands

    Gert N. Moll, Wil N. Konings & Arnold J. M. Driessen

  2. the Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN, Haren, the Netherlands

    Gert N. Moll, Wil N. Konings & Arnold J. M. Driessen

  3. Department of Biochemistry, University of Leicester, University Road, P.O. Box 138, LEI 9HN, Leicester, United Kingdom

    Gordon C. K. Roberts

  4. Biological NMR Centre, University of Leicester, University Road, P.O. Box 138, LE1 9HN, Leicester, United Kingdom

    Gordon C. K. Roberts

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  1. Gert N. Moll
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  3. Wil N. Konings
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  4. Arnold J. M. Driessen
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Moll, G.N., Roberts, G.C.K., Konings, W.N. et al. Mechanism of lantibiotic-induced pore-formation. Antonie van Leeuwenhoek 69, 185–191 (1996). https://doi.org/10.1007/BF00399423

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