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The Dependence of the Channel-Forming Ability of Lantibiotics on the Lipid Composition of the Membranes

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

The role of various membrane components, phospholipids and lipopolysaccharides, in the formation and functioning of ion channels formed by lantibiotics of class A, nisin, and class B, cinnamycin and duramycin, was studied. Threshold concentrations of the tested lantibiotics were determined that cause ion channel formation and destruction of planar lipid bilayers. It was found that nisin was able to form ion channels with a conductance in the range from 2 to 600 pS at a concentration of more than 40 μM both in negatively charged lipid bilayers containing a specific adjuvant of gram-negative bacterial membranes, Kdo2–lipid A, and in cardiolipin-containing membranes. The obtained results allowed suggesting that in model lipid membranes without lipid II, a precursor of peptidoglycan of gram-positive bacteria, which is a specific receptor of nisin, its role can be performed by Kdo2–lipid A and cardiolipin. It was found that cinnamycin and its close analogue duramycin at concentrations of 1.5–3 μM induced step-like current fluctuations corresponding to the functioning of single ion channels with amplitudes from 5 to 30 pS and from 50 to 900 pS in membranes of phosphatidylethanolamine and cardiolipin-enriched bilayers, respectively. Based on the results obtained, we conclude that the channel-forming ability of cinnamycin and duramycin depends on the presence in the membrane of lipids prone to the formation of inverted hexagonal phases and the induction of spontaneous negative curvature in lipid monolayers.

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REFERENCES

  1. Sahl H.G., Jack R.W., Bierbaum G. 1995. Biosynthesis and biological activities of lantibiotics with unique post-translational modifications. Eur. J. Biochem. 230, 827–853.

    Article  CAS  PubMed  Google Scholar 

  2. Sahl H.G., Bierbaum G. 1998. Lantibiotics: Biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria. Annu. Rev. Microbiol. 52, 41–79.

    Article  CAS  PubMed  Google Scholar 

  3. Jack R.W., Sahl H.G. 1995. Unique peptide modifications involved in the biosynthesis of lantibiotics. Trends Biotechnol. 13, 269–278.

    Article  CAS  PubMed  Google Scholar 

  4. McAuliffe O., Ross R.P., Hill C. 2001. Lantibiotics: Structure, biosynthesis and mode of action. FEMS Microbiol. Rev. 25, 285–308.

    Article  CAS  PubMed  Google Scholar 

  5. Willey J.M., van der Donk W.A. 2007. Lantibiotics: Peptides of diverse structure and function. Annu. Rev. Microbiol. 61, 477–501.

    Article  CAS  PubMed  Google Scholar 

  6. Knerr P.J., van der Donk W.A. 2012. Discovery, biosynthesis, and engineering of lantipeptides. Annu. Rev. Biochem. 81, 479–505.

    Article  CAS  PubMed  Google Scholar 

  7. Chatterjee C., Paul M., Xie L., van der Donk W.A. 2005. Biosynthesis and mode of action of lantibiotics. Chem. Rev. 105, 633–684.

    Article  CAS  PubMed  Google Scholar 

  8. Pag U., Sahl H.G. 2002. Multiple activities in lantibiotics—models for the design of novel antibiotics? Curr. Pharm. Des. 8, 815–833.

    Article  CAS  PubMed  Google Scholar 

  9. Gross E., Morell J.L. 1971. The structure of nisin. J. Am. Chem. Soc. 93, 4634–4635.

    Article  CAS  PubMed  Google Scholar 

  10. Li B., Yu J.P., Brunzelle J.S., Moll G.N., van der Donk W.A., Nair S.K. 2006. Structure and mechanism of the lantibiotic cyclase involved in nisin biosynthesis. Science. 311, 1464–1467.

    Article  CAS  PubMed  Google Scholar 

  11. Lubelski J., Rink R., Khusainov R., Moll G.N., Kuipers O.P. 2008. Biosynthesis, immunity, regulation, mode of action and engineering of the model lantibiotic nisin. Cell Mol. Life Sci. 65, 455–476.

    Article  CAS  PubMed  Google Scholar 

  12. Stevens K., Sheldon B., Klapes N., Klaenhammer T. 1991. Nisin treatment for inactivation of Salmonella species and other Gram-negative bacteria. Appl. Environ. Microbiol. 57, 3613–3615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Boziaris I., Adams M. 1999. Effect of chelators and nisin produced in situ on inhibition and inactivation of Gram-negatives. Int. J. Food Microbiol. 53, 105–113.

    Article  CAS  PubMed  Google Scholar 

  14. Chan W.C., Bycroft B.W., Lian L.Y., Roberts G.C. 1989. Isolation and characterisation of two degradation products derived from the peptide antibiotic nisin. FEBS Lett. 252, 29–36.

    Article  CAS  Google Scholar 

  15. Draper L.A., Cotter P.D., Hill C., Ross R.P. 2015. Lantibiotic resistance. Microbiol. Mol. Biol. Rev. 79, 171–191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wiedemann I., Breukink E., van Kraaij C., Kuipers O.P., Bierbaum G., de Kruijff B., Sahl H.G. 2001. Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity. J. Biol. Chem. 276, 1772–1779.

    Article  CAS  PubMed  Google Scholar 

  17. Van Heusden H.E., de Kruijff B., Breukink E. 2002. Lipid II induces a transmembrane orientation of the pore-forming peptide lantibiotic nisin. Biochem. 41, 12171–12178.

    Article  CAS  Google Scholar 

  18. Brötz H., Josten M., Wiedemann I., Schneider U., Götz F., Bierbaum G., Sahl H.G. 1998. Role of lipid-bound peptidoglycan precursors in the formation of pores by nisin, epidermin and other lantibiotics. Mol. Microbiol. 30, 317–327.

    Article  PubMed  Google Scholar 

  19. Breukink E., Wiedemann I., van Kraaij C., Kuipers O.P., Sahl H.G., de Kruijff B. 1999. Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science. 286, 2361–2364.

    Article  CAS  PubMed  Google Scholar 

  20. Prince A., Sandhu P., Ror P., Dash E., Sharma S., Arakha M., Jha S., Akhter Y., Saleem M. 2017. Lipid-II independent antimicrobial mechanism of nisin depends on its crowding and degree of oligomerization. Sci. Rep. 6, 37908.

    Article  CAS  Google Scholar 

  21. Joo N.E., Ritchie K., Kamarajan P., Miao D., Kapila Y.L. 2012. Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1. Cancer Med. 1, 295–305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rzeźnicka I.I., Sovago M., Backus E.H., Bonn M., Yamada T., Kobayashi T., Kawai M. 2010. Duramycin-induced destabilization of a phosphatidylethanolamine monolayer at the air-water interface observed by vibrational sum-frequency generation spectroscopy. Langmuir. 26, 16 055–16 062.

    Article  CAS  Google Scholar 

  23. Gomes K.M., Duarte R.S., de Freire Bastos M.D.C. 2017. Lantibiotics produced by Actinobacteria and their potential applications. Microbiology (Reading). 163, 109–121.

    Article  CAS  Google Scholar 

  24. Dunkley E.A.Jr, Clejan S., Guffanti A.A., Krulwich T.A. 1988. Large decreases in membrane phosphatidylethanolamine and diphosphatidylglycerol upon mutation to duramycin resistance do not change the protonophore resistance of Bacillus subtilis. Biochim. Biophys. Acta. 943, 13–18.

    Article  CAS  PubMed  Google Scholar 

  25. Machaidze G., Ziegler A., Seelig J. 2002. Specific binding of Ro 09-0198 (cinnamycin) to phosphatidylethanolamine: A thermodynamic analysis. Biochem. 41, 1965–1971.

    Article  CAS  Google Scholar 

  26. Kim S.E., Park J.W. 2019. Analysis of interactions between cinnamycin and biomimetic membranes. Colloids Surf. B Biointerfaces. 185, 110595.

    Article  PubMed  CAS  Google Scholar 

  27. Iwamoto K., Hayakawa T., Murate M., Makino A., Ito K., Fujisawa T., Kobayashi T. 2007. Curvature-dependent recognition of ethanolamine phospholipids by duramycin and cinnamycin. Biophys. J. 93, 1608–1619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chen L., Tai P.C. 1987. Effects of antibiotics and other inhibitors on ATP-dependent protein translocation into membrane vesicles. J. Bacteriol. 169, 2373–2379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sheth T.R., Henderson R.M., Hladky S.B., Cuthbert A.W. 1992. Ion channel formation by duramycin. Biochim. Biophys. Acta. 1107, 179–185.

    Article  CAS  PubMed  Google Scholar 

  30. Grasemann H., Stehling F., Brunar H., Widmann R., Laliberte T.W., Molina L., Döring G., Ratjen F. 2007. Inhalation of Moli1901 in patients with cystic fibrosis. Chest. 131, 1461–1466.

    Article  CAS  PubMed  Google Scholar 

  31. Ostroumova O.S., Efimova S.S., Schagina L.V. 2012. Probing amphotericin B single channel activity by membrane dipole modifiers. PLoS One 7, e30261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ostroumova O.S., Efimova S.S., Chulkov E.G., Schagina L.V. 2012. The interaction of dipole modifiers with polyene-sterol complexes. PLoS One 7, e45135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ostroumova O.S., Efimova S.S., Mikhailova E.V., Schagina L.V. 2014. The interaction of dipole modifiers with amphotericin-ergosterol complexes. Effects of phospholipid and sphingolipid membrane composition. Eur. Biophys. J. 43, 207–215.

    Article  CAS  PubMed  Google Scholar 

  34. Efimova S.S., Schagina L.V., Ostroumova O.S. 2014. Investigation of the channel-forming activity of polyene antibiotics in lipid bilayers using dipole modifiers. Acta Naturae (Rus.). 6 (4), 72–85.

    Google Scholar 

  35. Efimova S.S., Zakharova A.A., Schagina L.V., Ostroumova O.S. 2016. Two types of syringomycin E channels in sphingomyelin-containing bilayers. Eur. Biophys. J. 45, 91–98.

    Article  CAS  PubMed  Google Scholar 

  36. Efimova S.S., Zakharova A.A., Ismagilov A.A., Schagina L.V., Malev V.V., Bashkoriv P.V., Ostroumova O.S. 2018. Lipid-mediated regulation of pore-forming activity of syringomycin E by thyroid hormones and xanthene dyes. Biochim. Biophys. Acta. 1860, 691–699.

    Article  CAS  Google Scholar 

  37. Efimova S.S., Zakharova A.A., Medvedev R.Ya., Ostroumova O.S. 2018. Ion channels induced by antimicrobial agents in model lipid membranes are modulated by plant polyphenols through surrounding lipid media. J. Membr. Biol. 251, 551–562.

    Article  CAS  PubMed  Google Scholar 

  38. Zakharova A.A., Efimova S.S., Malev V.V., Ostroumova O.S. 2019. Fengycin induced ion channels on lipid bilayers mimicking target fungal cell membrane. Sci. Rep. 9, 16034.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Montal M., Muller P. 1972. Formation of bimolecular membranes from lipid monolayers and study of their electrical properties. Proc. Nat. Acad. Sci. USA. 65, 3561–3566.

    Article  Google Scholar 

  40. Gawrisch K., Holte L.L. 1996. NMR investigations of nonlamellar phase promoters in the lamellar phase state. Chem. Phys. Lipids. 81, 105–116.

    Article  CAS  Google Scholar 

  41. Kollmitzer B., Heftberger P., Rappolt M., Pabst G. 2013. Monolayer spontaneous curvature of raft-forming membrane lipids. Soft Matter. 9, 10 877–10 884.

    Article  CAS  Google Scholar 

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Funding

The work was supported by the Russian Science Foundation (project no. 19-14-00110).

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Authors and Affiliations

  1. Institute of Cytology Russian Academy of Science, 194064, St. Petersburg, Russia

    S. S. Efimova, E. V. Shekunov, D. N. Chernyshova, A. A. Zakharova & O. S. Ostroumova

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  1. S. S. Efimova
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  2. E. V. Shekunov
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  3. D. N. Chernyshova
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  4. A. A. Zakharova
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  5. O. S. Ostroumova
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Correspondence to S. S. Efimova.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by E. Puchkov

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Efimova, S.S., Shekunov, E.V., Chernyshova, D.N. et al. The Dependence of the Channel-Forming Ability of Lantibiotics on the Lipid Composition of the Membranes. Biochem. Moscow Suppl. Ser. A 16, 144–150 (2022). https://doi.org/10.1134/S1990747822020039

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  • DOI: https://doi.org/10.1134/S1990747822020039

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