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Antibacterial Activity and Synergism of the Hybrid Antimicrobial Peptide, CAMA-syn

  • Jeong, Ki-Woong (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Shin, So-Young (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Jin-Kyoung (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Yang-Mee (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University)
  • Published : 2009.08.20

Abstract

A 20-residue hybrid peptide CA(1-8)-MA(1-12) (CAMA) incorporating residues 1-8 of cecropin A (CA) and residues 1-12 of magainin 2 (MA) has high antimicrobial activity without toxicity. To investigate the effects of the total positive charges of CAMA on the antibacterial activity and toxicity, a hybrid peptide analogue (CAMA-syn) was designed with substitutions of $Ile^{10}\;and\;Ser^{16}$ with Lys. According to CD spectra, structure of CAMA-syn with increase of cationicity was very similar to that of CAMA in DPC micelle. CAMA-syn showed antimicrobial activity similar with CAMA while CAMA-syn has no hemolytic activity and much lower cytotoxicity against RAW 264.7 macrophage cells than CAMA. Also, CAMA and CAMA-syn significantly inhibited NO production by LPSstimulated RAW264.7 macrophage at 10.0∼20.0 $\mu$M. CAMA-syn displayed salt resistance on antimicrobial activity against Escherichia coli at the physiological concentrations of $CaCl_2\;and\;MgCl_2$. The combination studies of peptides and antibiotics showed that CAMA-syn has synergistic effects with synthetic compound and flavonoid against Enterococcus faecalis and VREF. CAMA-syn can be a good candidate for the development of new antibiotics with potent antibacterial and synergistic activity but without cytotoxicity.

Keywords

References

  1. Bevins, C. L.; Zasloff, M. Annu. Rev. Biochem. 1990, 59, 395 https://doi.org/10.1146/annurev.bi.59.070190.002143
  2. Hancock, R. E.; Rozek, A. FEMS Microbiol. Lett. 2002, 206, 143 https://doi.org/10.1111/j.1574-6968.2002.tb11000.x
  3. Boman, H. G. Annu. Rev. Immunol. 1995, 13, 61 https://doi.org/10.1146/annurev.iy.13.040195.000425
  4. Maloy, W. L.; Kari, U. P. Biopolymers (Pept. Sci.) 1995, 37, 105 https://doi.org/10.1002/bip.360370206
  5. Hancock, R. E. Lancet 1997, 349, 418 https://doi.org/10.1016/S0140-6736(97)80051-7
  6. Andreu, D.; Rivas, L. Biopolymers (Pept. Sci.) 1998, 47, 415 https://doi.org/10.1002/(SICI)1097-0282(1998)47:6<415::AID-BIP2>3.0.CO;2-D
  7. Oren, Z.; Shai, Y. Biopolymers (Pept. Sci.) 1998, 47, 451 https://doi.org/10.1002/(SICI)1097-0282(1998)47:6<451::AID-BIP4>3.0.CO;2-F
  8. Miyasaki, K.; Lehrer, R. I. Int. J. Antimicrob. Agents 1998, 9, 269 https://doi.org/10.1016/S0924-8579(98)00006-5
  9. Lehrer, R. I.; Ganz, T. Curr. Opin. in Immunol. 1999, 11, 23 https://doi.org/10.1016/S0952-7915(99)80005-3
  10. Hancock, R. E.; Chapple, D. Antimicrob. Agents Chemother. 1999, 43, 1317
  11. Miyasaki, K.; Lehrer, R. I. Int. J. Antimicrob. Agents 1998, 9, 269 https://doi.org/10.1016/S0924-8579(98)00006-5
  12. Lehrer, R. I.; Ganz, T. Curr. Opin. in Immunol. 1999, 11, 23 https://doi.org/10.1016/S0952-7915(99)80005-3
  13. Zasloff, M. Proc. Natl. Acad. Sci. U. S. A. 1987, 84, 5449 https://doi.org/10.1073/pnas.84.15.5449
  14. Steiner, H.; Hultmark, D.; Engstrom, A.; Bennich, H.; Boman, H. G. Nature 1981, 292, 246 https://doi.org/10.1038/292246a0
  15. Lee, J. Y.; Boman, A.; Sun, C.; Andersson, M.; Jornvall, H.; Mutt, V.; Boman, H. G. Proc. Natl. Acad. Sci. U. S. A. 1989, 86, 9195
  16. Shin, S. Y.; Lee, M. K.; Kim, K. L.; Hahm, K. S. J. Peptide Res. 1997, 50, 279
  17. Shin, S. Y.; Kang, J. H.; Lee, M. K.; Kim, S. Y.; Kim, Y.; Hahm, K. S. Biochem. Mol. Biol. Int. 1998, 44, 1119
  18. Shin, S. Y.; Kang, J. H.; Hahm, K. S. J. Peptide Res. 1999, 53, 82 https://doi.org/10.1111/j.1399-3011.1999.tb01620.x
  19. Oh, D.; Shin, S. Y.; Kang, J. H.; Hahm, K. S.; Kim, Y. J. Pept. Res. 1999, 53, 578 https://doi.org/10.1034/j.1399-3011.1999.00067.x
  20. Oh, D.; Shin, S. Y.; Lee, S.; Kang, J. H.; Kim, S. D.; Ryu, P. D.; Hahm, K. S.; Kim, Y. Biochemistry 2000, 39, 11855 https://doi.org/10.1021/bi000453g
  21. Shin, S. Y.; Yang, S. T.; Park, E. J.; Eom, S. H.; Song, W. K.; Kim, Y.; Hahm, K. S.; Kim, J. I. Biochem. Biophys. Res. Commun. 2002, 290, 558 https://doi.org/10.1006/bbrc.2001.6234
  22. Park. Y.; Park, S. N.; Park, S. C.; Shin, S. O.; Kim, J. Y.; Kang, S. J.; Kim, M. H.; Jeong, C. Y.; Hahm, K. S. Biochim. Biophys. Acta 2006, 1764, 24 https://doi.org/10.1016/j.bbapap.2005.10.019
  23. Giacometti, A.; Cirioni, O.; Barchiesi, F.; Fortuna, M.; Scalise, G. J. Antimicrob. Chemother. 1999, 44, 642
  24. Giacometti, A.; Cirioni, O.; Del Prete, M. S.; Paggi, A. M.; D'Errico, M. M.; Scalise, G. J. Antimicrob. Agents Chemother. 2000, 21, 1155
  25. Graham, S.; Coote, P. J. J. Antimicrob. Chemother. 2007, 59, 759 https://doi.org/10.1093/jac/dkl539
  26. Yeo, I. Y.; Koo, B. K.; Oh, E. S.; Han, I. O.; Lee, W. Bull. Korean Chem. Soc. 2008, 29, 1013 https://doi.org/10.5012/bkcs.2008.29.5.1013
  27. Woo, S.; Kang, D. H.; Kim, J.; Lee, C. S.; Lee, E. S.; Jahng, Y.; Kwon, Y.; Na, Y. Bull. Korean Chem. Soc. 2008, 29, 471 https://doi.org/10.5012/bkcs.2008.29.2.471
  28. Scudiero, D. A.; Shoemaker, R. H.; Paull, K. D.; Monks, A.; Tierney, S.; Nofziger, T. H.; Currens, M. J.; Seniff, D.; Boyd, M. R. Cancer Res. 1988, 48, 482733
  29. Green, L. C.; Wagner, D. A.; Glogowski, J.; Skipper, P. L.; Wishnok, J. S.; Tannenbaum, S. R. Anal. Biochem. 1982, 126, 131 https://doi.org/10.1016/0003-2697(82)90118-X
  30. Jeong, K. W.; Lee, J. Y.; Kim, Y. Bull. Korean Chem. Soc. 2007, 28, 1335 https://doi.org/10.5012/bkcs.2007.28.8.1335
  31. Klastersky, J.; Cappel, R.; Daneau, D. Antimicrob. Agents Chemother. 1972, 2, 470 https://doi.org/10.1128/AAC.2.6.470
  32. Eliopoulos, G. M.; Moellering, R. C. Antimicrobial Combinations; Williams and Wilkins: Baltimore, MD, 1996; pp 432-492
  33. White, R. L.; Burgess, D. S.; Manduru, M. Bosso, J. A. Antimicrob. Agents Chemother. 1996, 40, 1914
  34. Lee, S. A.; Kim, Y. K.; Lim, S. S.; Zhu, L. W.; Ko, H.; Shin, S. Y.; Hahm, K. S.; Kim, Y. Biochemistry 2007, 46, 3653 https://doi.org/10.1021/bi062233u
  35. Hopp, T. P.; Woods, K. R. Proc. Natl. Acad. Sci. U. S. A. 1981, 78, 3824 https://doi.org/10.1073/pnas.78.6.3824
  36. Goldman, M. J.; Anderson, G. M.; Stolzenberg, E. D.; Kari, D. P.; Zasloff, M. K.; Wilson, J. M. Cell 1997, 88, 553 https://doi.org/10.1016/S0092-8674(00)81895-4
  37. Piers, K. L.; Brown, M. H.; Hancock, R. E. W. Antimicrob. Agents Chemother. 1994, 38, 2311 https://doi.org/10.1128/AAC.38.10.2311
  38. Cole, A. M.; Darouiche, R. O.; Legarda, D.; Connell, N.; Diamond, G. Antimicrob. Agents Chemother. 1987, 44, 2039 https://doi.org/10.1128/AAC.44.8.2039-2045.2000
  39. Jeong, K. W.; Lee, J. Y.; Kang, D. I.; Lee, J. U.; Shim, S. Y.; Kim, Y. J. Nat. Prod. 2009, 72, 719 https://doi.org/10.1021/np800698d
  40. Lee, J. Y.; Jeong, K. W.; Lee, J. U.; Kang, D. I.; Kim, Y. Bioorg. Med. Chem. 2009, 17, 1506 https://doi.org/10.1016/j.bmc.2009.01.004
  41. George, A. M. FEMS Microbiol. Lett. 1996, 139, 1 https://doi.org/10.1111/j.1574-6968.1996.tb08172.x
  42. Hancock, R. E. W. Clin. Infect. Dis. 1998, 27, S93 https://doi.org/10.1086/514909
  43. Noskin, G. A. J. Lab. Clin. Med. 1997, 130, 14 https://doi.org/10.1016/S0022-2143(97)90054-8
  44. Rice, L. B. Emerg. Infect. Dis. 2001, 7, 183 https://doi.org/10.3201/eid0702.010205
  45. Linden, P. K.; Miller, C. B. Diagn. Microbiol. Infect. Dis. 1999, 33, 113 https://doi.org/10.1016/S0732-8893(98)00148-5
  46. Odds, F. C. J. Antimicrob. Chemother. 2003, 52, 1 https://doi.org/10.1093/jac/dkg301
  47. Pag, U.; Oedenkoven, M.; Papo, N.; Oren, Z.; Shai, Y.; Sahl, H. G. J. Antimicrob. Chemother. 2004, 53, 230 https://doi.org/10.1093/jac/dkh083

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