1887

Abstract

The human-mediated use and abuse of classical antibiotics has created a strong selective pressure for the rapid evolution of antibiotic resistance. As resistance levels rise, and the efficacy of classical antibiotics wanes, the intensity of the search for alternative antimicrobials has increased. One class of molecules that has attracted much attention is the antimicrobial peptides (AMPs). They exhibit broad-spectrum activity, they are potent and they are widespread as part of the innate defence system of both vertebrates and invertebrates. However, peptides are complex molecules that suffer from proteolytic degradation. The ability to capture the essential properties of antimicrobial peptides in simple easy-to-prepare molecules that are abiotic in origin and non-proteolytic offers many advantages. Mechanistic and structural knowledge of existing AMPs was used to design a novel compound that mimics the biochemical activity of an AMP. This report describes the development and characterization of a small peptide mimic that exhibited quick-acting and selective antibacterial activity against a broad range of bacteria, including numerous clinically relevant strains, at low MIC values.

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2006-07-01
2019-11-21
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References

  1. Andreu, D. & Rivas, L. ( 1998; ). Animal antimicrobial peptides: an overview. Biopolymers 47, 415–433.[CrossRef]
    [Google Scholar]
  2. Arnt, L. & Tew, G. N. ( 2002; ). New poly(phenyleneethynylene)s with cationic, facially amphiphilic structures. J Am Chem Soc 124, 7664–7665.[CrossRef]
    [Google Scholar]
  3. Arnt, L., Nüsslein, K. & Tew, G. N. ( 2004; ). Nonhemolytic abiogenic polymers as antimicrobial peptide mimics. J Polymer Sci A Polymer Chem 42, 3860–3864.[CrossRef]
    [Google Scholar]
  4. Barry, A. L. ( 1976; ). The Antimicrobic Susceptibility Test: Principles and Practice. Philadelphia, PA: Lea & Feliger.
  5. Broekaert, W. E. F., Cammue, B. P. A., De Bolle, M. F. C., Thevissen, K., De Samblanx, G. W. & Osborn, R. W. ( 1997; ). Antimicrobial peptides from plants. Crit Rev Plant Sci 16, 297–323.[CrossRef]
    [Google Scholar]
  6. Bucki, R., Pastore, J. J., Randhawa, P., Vegners, R., Weiner, D. J. & Janmey, P. A. ( 2004; ). Antibacterial activities of rhodamine B-conjugated gelsolin-derived peptides compared to those of the antimicrobial peptides cathelicidin LL37, magainin II, and melittin. Antimicrob Agents Chemother 48, 1526–1533.[CrossRef]
    [Google Scholar]
  7. Bulet, P., Hetru, C., Dimarcq, J. L. & Hoffmann, D. ( 1999; ). Antimicrobial peptides in insects; structure and function. Dev Comp Immunol 23, 329–344.[CrossRef]
    [Google Scholar]
  8. Dixon, R. A. & Chopra, I. ( 1986; ). Polymyxin B and polymyxin B nonapeptide alter cytoplasmic membrane permeability in Escherichia coli. J Antimicrob Chemother 18, 557–563.[CrossRef]
    [Google Scholar]
  9. Guerrero, E., Saugar, J. M., Matsuzaki, K. & Rivas, L. ( 2004; ). Role of positional hydrophobicity in the leishmanicidal activity of magainin 2. Antimicrob Agents Chemother 48, 2980–2986.[CrossRef]
    [Google Scholar]
  10. Hancock, R. E. W. & Chapple, D. S. ( 1999; ). Peptide antibiotics. Antimicrob Agents Chemother 42, 1317–1323.
    [Google Scholar]
  11. Hancock, R. E. W. & Diamond, G. ( 2000; ). The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol 8, 402–410.[CrossRef]
    [Google Scholar]
  12. Huang, H. W. ( 2000; ). Action of antimicrobial peptides: two-state model. Biochemistry 39, 8347–8352.[CrossRef]
    [Google Scholar]
  13. Kohli, R. M., Walsh, C. T. & Burkart, M. D. ( 2002; ). Biomimetic synthesis and optimization of cyclic peptide antibiotics. Nature 418, 658–661.[CrossRef]
    [Google Scholar]
  14. Li, C., Budge, L. P., Driscoll, C. D., Willardson, B. M., Allman, G. W. & Savage, P. B. ( 1999; ). Incremental conversion of outer-membrane permeabilizers into potent antibiotics for Gram-negative bacteria. J Am Chem Soc 121, 931–940.[CrossRef]
    [Google Scholar]
  15. Liu, D., Choi, S., Chen, B., Doerksen, R. J., Clements, D. J., Winkler, J. D., Klein, M. L. & DeGrado, W. F. ( 2004; ). Nontoxic membrane-active antimicrobial arylamide oligomers. Angew Chem Int Ed Engl 43, 1158–1162.[CrossRef]
    [Google Scholar]
  16. Monner, A., Jonsson, S. & Boman, H. G. ( 1971; ). Ampicillin-resistant mutanys of Escherichia coli K-12 with lipopolysaccharide. J Bacteriol 107, 420–432.
    [Google Scholar]
  17. National Committee for Clinical Laboratory Standards ( 1999; ). Methods for Determining Bactericidal Activity of Antimicrobial Agents; Approved Guideline. Document M26-A. Wayne, PA: National Committee for Clinical Laboratory Standards.
  18. National Committee for Clinical Laboratory Standards ( 2003; ). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, 6th edn. Document M7-A6. Wayne, PA: National Committee for Clinical Laboratory Standards.
  19. Porter, E. A., Wang, X., Lee, H. S., Weisblum, B. & Gellman, S. H. ( 2000; ). Non-haemolytic beta-amino acid oligomers. Nature 404, 565.[CrossRef]
    [Google Scholar]
  20. Shai, Y. & Oren, Z. ( 2001; ). From ‘carpet’ mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides. Peptides 22, 1629–1641.[CrossRef]
    [Google Scholar]
  21. Steinberg, D. A., Hurst, M. A., Fujii, C. A., Kung, A. H., Ho, J. F., Cheng, F. C., Loury, D. J. & Fiddes, J. C. ( 1997; ). Protegrin-1: a broad-spectrum, rapidly microbicidal peptide with in vivo activity. Antimicrob Agents Chemother 41, 1738–1742.
    [Google Scholar]
  22. Strøm, M. B., Haug, B. E., Skar, M. L., Stensen, W., Stiberg, T. & Svendsen, J. S. ( 2003; ). The pharmacophore of short cationic antibacterial peptides. J Med Chem 46, 1567–1570.[CrossRef]
    [Google Scholar]
  23. Tamayo, R., Portillo, A. C. & Gunn, J. S. ( 2004; ). Mechanisms of bacterial resistance to antimicrobial peptides. In Mammalian Host Defense Peptides, pp. 323–348. Edited by D. A. Devine & R. E. W. Hancock. Cambridge: Cambridge University Press.
  24. Tew, G. N., Liu, D., Chen, B., Doerksen, R. J., Kaplan, J., Carroll, P. J., Klein, M. L. & DeGrado, W. F. ( 2002; ). De novo design of biomimetic antimicrobial polymers. Proc Natl Acad Sci U S A 99, 5110–5114.[CrossRef]
    [Google Scholar]
  25. Toke, O. ( 2005; ). Antimicrobial peptides: new candidates in the fight against bacterial infections. Biopolymers 80, 717–735.[CrossRef]
    [Google Scholar]
  26. Walsh, C. ( 2003; ). Antibiotics: Actions, Origins, Resistance. Washington, DC: American Society for Microbiology.
  27. Wu, M., Maier, E., Benz, R. & 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.[CrossRef]
    [Google Scholar]
  28. Yeaman, M. R., Gank, K. D., Bayer, A. S. & Brass, E. P. ( 2002; ). Synthetic peptides that exert antimicrobial activities in whole blood and blood-derived matrices. Antimicrob Agents Chemother 46, 3883–3891.[CrossRef]
    [Google Scholar]
  29. Yount, N. Y. & Yeaman, M. R. ( 2005; ). Multidimensional signatures in antimicrobial peptides. Proc Natl Acad Sci U S A 101, 7363–7368.
    [Google Scholar]
  30. Zasloff, M. ( 2002; ). Antimicrobial peptides of multicellular organisms. Nature 415, 389.[CrossRef]
    [Google Scholar]
  31. Zhang, L., Rozek, A. & Hancock, R. E. ( 2001; ). Interaction of cationic antimicrobial peptides with model membranes. J Biol Chem 276, 35714–35722.[CrossRef]
    [Google Scholar]
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vol. , part 7, pp. 1913-1918

Table S1. tests of antimicrobial activities against a group of selected bacterial species of the peptide mimic mPE after 6 and 20 h, and its selectivity index.



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