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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Different modes of antibiotic action of homodimeric and monomeric bactenecin, a cathelicidin-derived antibacterial peptide

  • Lee, Ju-Yeon (Department of Life Science, Research Center for Bio-imaging, Gwangju Institute of Science and Technology) ;
  • Yang, Sung-Tae (Department of Life Science, Research Center for Bio-imaging, Gwangju Institute of Science and Technology) ;
  • Kim, Hyo-Jeong (Department of Life Science, Research Center for Bio-imaging, Gwangju Institute of Science and Technology) ;
  • Lee, Seung-Kyu (Department of Life Science, Research Center for Bio-imaging, Gwangju Institute of Science and Technology) ;
  • Jung, Hyun-Ho (Department of Life Science, Research Center for Bio-imaging, Gwangju Institute of Science and Technology) ;
  • Shin, Song-Yub (Department of Bio-Materials, Graduate School and Department of Cellular & Molecular Medicine, School of Medicine, Chosun University) ;
  • Kim, Jae-Il (Department of Life Science, Research Center for Bio-imaging, Gwangju Institute of Science and Technology)
  • Published : 2009.09.30
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Abstract

The bactenecin is an antibacterial peptide with an intramolecular disulfide bond. We recently found that homodimeric bactenecin exhibits more potent antibacterial activity than the monomeric form and retains its activity at physiological conditions. Here we assess the difference in the modes of antibiotic action of homodimeric and monomeric bactenecins. Both monomeric and dimeric bactenecins almost completely killed both Staphylococcus aureus and E. coli within 10-30 min at concentrations of $8-16\;{\mu}M$. However, exposure to liposomes elicited an increase in the fluorescence quantum yield from a tryptophan-containing monomeric analog, while the homodimeric analog showed a significant reduction in fluorescence intensity. Moreover, unlike the monomer, the homodimer displayed apparent membrane-lytic activity enabling release of various sized dyes from liposomes, and rapidly and fully depolarized the S. aureus membrane. Together, our results suggest that homodimeric bactenecin forms pores in the bacterial membrane, while monomeric one penetrates through the membrane to target intracellular molecules/organelles.

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References

  1. Zasloff, M. (2002) Antimicrobial peptides of multicellular organisms. Nature 415, 389-395 https://doi.org/10.1038/415389a
  2. Andreu, D. and Rivas, L. (1998) Animal antimicrobial peptides: an overview. Biopolymers 47, 415-433 https://doi.org/10.1002/(SICI)1097-0282(1998)47:6<415::AID-BIP2>3.0.CO;2-D
  3. Koczulla, A. R. and Bals, R. (2003) Antimicrobial peptides: current status and therapeutic potential. Drugs 63, 389-406 https://doi.org/10.2165/00003495-200363040-00005
  4. Matsuzaki, K. (2008) Control of cell selectivity of antimicrobial peptides. Biochim. Biophys. Acta (in press)
  5. Brogden, K. A. (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3, 238-250 https://doi.org/10.1038/nrmicro1098
  6. Yeaman, M. R. and Yount, N. Y. (2003) Mechanisms of antimicrobial peptide action and resistance. Pharmacol. Rev. 55, 27-55
  7. Papo, N. and Shai, Y. (2003) Can we predict biological activity of antimicrobial peptides from their interactions with model phospholipid membranes? Peptides 24, 1693-1703 https://doi.org/10.1016/j.peptides.2003.09.013
  8. Shai, Y. (2002) Mode of action of membrane active antimicrobial peptides. Biopolymers 66, 236-248 https://doi.org/10.1002/bip.10260
  9. Cudic, M. and Otvos, L. Jr. (2002) Intracellular targets of antibacterial peptides. Curr. Drug Targets 3, 101-106 https://doi.org/10.2174/1389450024605445
  10. Yang, S. T., Shin, S. Y., Hahm, K. S. and Kim, J. I. (2006) Different modes in antibiotic action of tritrpticin analogs, cathelicidin-derived Trp-rich and Pro/Arg-rich peptides. Biochim. Biophys. Acta 1758, 1580-1586 https://doi.org/10.1016/j.bbamem.2006.06.007
  11. Podda, E., Benincasa, M., Pacor, S., Micali, F., Mattiuzzo, M., Gennaro, R. and Scocchi, M. (2006) Dual mode of action of Bac7, a proline-rich antibacterial peptide. Biochim. Biophys. Acta 1760, 1732-1740 https://doi.org/10.1016/j.bbagen.2006.09.006
  12. Romeo, D., Skerlavaj, B., Bolognesi, M. and Gennaro, R. (1988) Structure and bactericidal activity of an antibiotic dodecapeptide purified from bovine neutrophils. J .Biol. Chem. 263, 9573-9575
  13. Wu, M. and Hancock, R. E. W. (1999) Interaction of the cyclic antimicrobial cationic peptide bactenecin with the outer and cytoplasmic membrane. J. Biol. Chem. 274, 29-35 https://doi.org/10.1074/jbc.274.1.29
  14. Gennaro, R., Skerlavaj, B. and Romeo, D. (1989) Purification, composition, and activity of two bactenecins, antibacterial peptides of bovine neutrophils. Infect. Immun. 57, 3142-3146
  15. Wu, M. and Hancock, R. E. W. (1999) Improved derivatives of bactenecin, a cyclic dodecameric antimicrobial cationic peptide. Antimicrob. Agents Chemother. 43, 1274-1276
  16. Storici, P., Tossi, A., Lenarcic, B. and Romeo, D. (1996) Purification and structural characterization of bovine cathelicidins, precursors of antimicrobial peptides. Eur. J. Biochem. 238, 769-776 https://doi.org/10.1111/j.1432-1033.1996.0769w.x
  17. Lee, J. Y., Yang, S. T., Lee, S. K., Jung, H. H., Shin, S. Y., Hahm, K. S. and Kim, J. I. (2008) Salt-resistant homodimeric bactenecin, a cathelicidin-derived antimicrobial peptide. FEBS J. 275, 3911-3920 https://doi.org/10.1111/j.1742-4658.2008.06536.x
  18. Wu, M., Maier, E., Benz, R. and Hancock, R. E. W. (1999) Mechanism of interaction of different classes of cationic antimicrobial peptides with planar bilayers and with the cytoplasmic membrane of Escherichia coli. Biochemistry 38, 7235-7242 https://doi.org/10.1021/bi9826299
  19. Lakoxicz, J. R. (1999) Principles of Fluorescence Spectroscopy, 2nd ed., Kluwer Academic/Plenum, New York, USA
  20. Zelezetsky, I., Pontillo, A., Puzzi, L., Antcheva, N., Segat, L., Pacor, S., Crovella, S. and Tossi, A. (2006) Evolution of the primate cathelicidin. Correlation between structural variations and antimicrobial activity. J. Biol. Chem. 281, 19861-19871 https://doi.org/10.1074/jbc.M511108200
  21. Breukink, E., van Kraaij, C., van Dalen, A., Demel, R. A., Siezen, R. J., de Kruijff, B. and Kuipers, O. P. (1998) The orientation of nisin in membranes. Biochemistry 37, 8153-8162 https://doi.org/10.1021/bi972797l
  22. Zhao, H. and Kinnunen, P. K. (2002) Binding of the antimicrobial peptide temporin L to liposomes assessed by Trp fluorescence. J. Biol. Chem. 277, 25170-25177 https://doi.org/10.1074/jbc.M203186200
  23. Christiaens, B., Symoens, S., Verheyden, S., Engelborghs, Y., Joliot, A., Prochiantz, A., Vandekerckhove, J., Rosseneu, M. and Vanloo, B. (2002) Tryptophan fluorescence study of the interaction of penetratin peptides with model membranes. Eur. J. Biochem. 269, 2918-2926 https://doi.org/10.1046/j.1432-1033.2002.02963.x
  24. Zhu, W. L. and Shin, S. Y. (2009) Effects of dimerization of the cell-penetrating peptide Tat analog on antimicrobial activity and mechanism of bactericidal action. J. Pept. Sci. 15, 345-352 https://doi.org/10.1002/psc.1120
  25. Zhu, W. L. and Shin, S. Y. (2009) Antimicrobial and cytolytic activities and plausible mode of bactericidal action of the cell penetrating peptide penetratin and its lys-linked two-stranded peptide. Chem. Biol. Drug Des. 73, 209-215 https://doi.org/10.1111/j.1747-0285.2008.00769.x
  26. Szoka, F. Jr. and Papahadjopoulos, D. (1978) Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc. Natl. Acad. Sci. U.S.A. 75, 4194-4198 https://doi.org/10.1073/pnas.75.9.4194

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