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. 1997 Apr;41(4):771–775. doi: 10.1128/aac.41.4.771

Improved activity of a synthetic indolicidin analog.

T J Falla 1, R E Hancock 1
PMCID: PMC163792  PMID: 9087487

Abstract

A novel cationic peptide, CP-11, based on the structure of the bovine neutrophil peptide indolicidin, was designed to increase the number of positively charged residues, maintain the short length (13 amino acids), and enhance the amphipathicity relative to those of indolicidin. CP-11, and especially its carboxymethylated derivative, CP-11C, demonstrated improved activity against gram-negative bacteria and Candida albicans, while it maintained the activity of indolicidin against staphylococci and demonstrated a reduced ability to lyse erythrocytes. In Escherichia coli, CP-11 was better able than indolicidin to permeabilize both the outer membrane, as indicated by the enhancement of uptake of 1-N-phenylnaphthylamine, and the inner membrane, as determined by the unmasking of cytoplasmic beta-galactosidase, providing an explanation for its improved activity.

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Selected References

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  1. Agerberth B., Lee J. Y., Bergman T., Carlquist M., Boman H. G., Mutt V., Jörnvall H. Amino acid sequence of PR-39. Isolation from pig intestine of a new member of the family of proline-arginine-rich antibacterial peptides. Eur J Biochem. 1991 Dec 18;202(3):849–854. doi: 10.1111/j.1432-1033.1991.tb16442.x. [DOI] [PubMed] [Google Scholar]
  2. Ahmad I., Perkins W. R., Lupan D. M., Selsted M. E., Janoff A. S. Liposomal entrapment of the neutrophil-derived peptide indolicidin endows it with in vivo antifungal activity. Biochim Biophys Acta. 1995 Jul 26;1237(2):109–114. doi: 10.1016/0005-2736(95)00087-j. [DOI] [PubMed] [Google Scholar]
  3. Aley S. B., Zimmerman M., Hetsko M., Selsted M. E., Gillin F. D. Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides. Infect Immun. 1994 Dec;62(12):5397–5403. doi: 10.1128/iai.62.12.5397-5403.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Andreu D., Merrifield R. B., Steiner H., Boman H. G. N-terminal analogues of cecropin A: synthesis, antibacterial activity, and conformational properties. Biochemistry. 1985 Mar 26;24(7):1683–1688. doi: 10.1021/bi00328a017. [DOI] [PubMed] [Google Scholar]
  5. Angus B. L., Carey A. M., Caron D. A., Kropinski A. M., Hancock R. E. Outer membrane permeability in Pseudomonas aeruginosa: comparison of a wild-type with an antibiotic-supersusceptible mutant. Antimicrob Agents Chemother. 1982 Feb;21(2):299–309. doi: 10.1128/aac.21.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bessalle R., Haas H., Goria A., Shalit I., Fridkin M. Augmentation of the antibacterial activity of magainin by positive-charge chain extension. Antimicrob Agents Chemother. 1992 Feb;36(2):313–317. doi: 10.1128/aac.36.2.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blondelle S. E., Houghten R. A. Hemolytic and antimicrobial activities of the twenty-four individual omission analogues of melittin. Biochemistry. 1991 May 14;30(19):4671–4678. doi: 10.1021/bi00233a006. [DOI] [PubMed] [Google Scholar]
  8. Falla T. J., Karunaratne D. N., Hancock R. E. Mode of action of the antimicrobial peptide indolicidin. J Biol Chem. 1996 Aug 9;271(32):19298–19303. doi: 10.1074/jbc.271.32.19298. [DOI] [PubMed] [Google Scholar]
  9. Fields P. I., Groisman E. A., Heffron F. A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells. Science. 1989 Feb 24;243(4894 Pt 1):1059–1062. doi: 10.1126/science.2646710. [DOI] [PubMed] [Google Scholar]
  10. Gennaro R., Skerlavaj B., Romeo D. Purification, composition, and activity of two bactenecins, antibacterial peptides of bovine neutrophils. Infect Immun. 1989 Oct;57(10):3142–3146. doi: 10.1128/iai.57.10.3142-3146.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hancock R. E., Carey A. M. Outer membrane of Pseudomonas aeruginosa: heat- 2-mercaptoethanol-modifiable proteins. J Bacteriol. 1979 Dec;140(3):902–910. doi: 10.1128/jb.140.3.902-910.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hancock R. E., Falla T., Brown M. Cationic bactericidal peptides. Adv Microb Physiol. 1995;37:135–175. doi: 10.1016/s0065-2911(08)60145-9. [DOI] [PubMed] [Google Scholar]
  13. Hancock R. E., Raffle V. J., Nicas T. I. Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1981 May;19(5):777–785. doi: 10.1128/aac.19.5.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lehrer R. I., Barton A., Daher K. A., Harwig S. S., Ganz T., Selsted M. E. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest. 1989 Aug;84(2):553–561. doi: 10.1172/JCI114198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Loh B., Grant C., Hancock R. E. Use of the fluorescent probe 1-N-phenylnaphthylamine to study the interactions of aminoglycoside antibiotics with the outer membrane of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1984 Oct;26(4):546–551. doi: 10.1128/aac.26.4.546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Piers K. L., Brown M. H., Hancock R. E. Improvement of outer membrane-permeabilizing and lipopolysaccharide-binding activities of an antimicrobial cationic peptide by C-terminal modification. Antimicrob Agents Chemother. 1994 Oct;38(10):2311–2316. doi: 10.1128/aac.38.10.2311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Piers K. L., Hancock R. E. The interaction of a recombinant cecropin/melittin hybrid peptide with the outer membrane of Pseudomonas aeruginosa. Mol Microbiol. 1994 Jun;12(6):951–958. doi: 10.1111/j.1365-2958.1994.tb01083.x. [DOI] [PubMed] [Google Scholar]
  18. Richmond M. H., Clark D. C., Wotton S. Indirect method for assessing the penetration of beta-lactamase-nonsusceptible penicillins and cephalosporins in Escherichia coli strains. Antimicrob Agents Chemother. 1976 Aug;10(2):215–218. doi: 10.1128/aac.10.2.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sawyer J. G., Martin N. L., Hancock R. E. Interaction of macrophage cationic proteins with the outer membrane of Pseudomonas aeruginosa. Infect Immun. 1988 Mar;56(3):693–698. doi: 10.1128/iai.56.3.693-698.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schluesener H. J., Radermacher S., Melms A., Jung S. Leukocytic antimicrobial peptides kill autoimmune T cells. J Neuroimmunol. 1993 Sep;47(2):199–202. doi: 10.1016/0165-5728(93)90030-3. [DOI] [PubMed] [Google Scholar]
  21. Selsted M. E., Novotny M. J., Morris W. L., Tang Y. Q., Smith W., Cullor J. S. Indolicidin, a novel bactericidal tridecapeptide amide from neutrophils. J Biol Chem. 1992 Mar 5;267(7):4292–4295. [PubMed] [Google Scholar]
  22. Yasin B., Lehrer R. I., Harwig S. S., Wagar E. A. Protegrins: structural requirements for inactivating elementary bodies of Chlamydia trachomatis. Infect Immun. 1996 Nov;64(11):4863–4866. doi: 10.1128/iai.64.11.4863-4866.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Zanetti M., Gennaro R., Romeo D. Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett. 1995 Oct 23;374(1):1–5. doi: 10.1016/0014-5793(95)01050-o. [DOI] [PubMed] [Google Scholar]

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