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.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.28812-0
2006-07-01
2020-07-09
Loading full text...

Full text loading...

/deliver/fulltext/micro/152/7/1913.html?itemId=/content/journal/micro/10.1099/mic.0.28812-0&mimeType=html&fmt=ahah

References

  1. Andreu D, Rivas L. 1998; Animal antimicrobial peptides: an overview. Biopolymers47:415–433[CrossRef]
    [Google Scholar]
  2. Arnt L, Tew G. N. 2002; New poly(phenyleneethynylene)s with cationic, facially amphiphilic structures. J Am Chem Soc124:7664–7665[CrossRef]
    [Google Scholar]
  3. Arnt L, Tew G. N, Nüsslein K. 2004; Nonhemolytic abiogenic polymers as antimicrobial peptide mimics. J Polymer Sci A Polymer Chem42:3860–3864[CrossRef]
    [Google Scholar]
  4. Barry A. L. 1976; The Antimicrobic Susceptibility Test: Principles and Practice Philadelphia, PA: Lea & Feliger;
    [Google Scholar]
  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 Sci16:297–323[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 Chemother48:1526–1533[CrossRef]
    [Google Scholar]
  7. Bulet P, Hetru C, Dimarcq J. L, Hoffmann D. 1999; Antimicrobial peptides in insects; structure and function. Dev Comp Immunol23:329–344[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 Chemother18:557–563[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 Chemother48:2980–2986[CrossRef]
    [Google Scholar]
  10. Hancock R. E. W, Chapple D. S. 1999; Peptide antibiotics. Antimicrob Agents Chemother42:1317–1323
    [Google Scholar]
  11. Hancock R. E. W, Diamond G. 2000; The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol8:402–410[CrossRef]
    [Google Scholar]
  12. Huang H. W. 2000; Action of antimicrobial peptides: two-state model. Biochemistry39:8347–8352[CrossRef]
    [Google Scholar]
  13. Kohli R. M, Walsh C. T, Burkart M. D. 2002; Biomimetic synthesis and optimization of cyclic peptide antibiotics. Nature418:658–661[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 Soc121:931–940[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 Engl43:1158–1162[CrossRef]
    [Google Scholar]
  16. Monner A, Jonsson S, Boman H. G. 1971; Ampicillin-resistant mutanys of Escherichia coli K-12 with lipopolysaccharide. J Bacteriol107:420–432
    [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;
    [Google Scholar]
  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;
    [Google Scholar]
  19. Porter E. A, Wang X, Lee H. S, Weisblum B, Gellman S. H. 2000; Non-haemolytic beta-amino acid oligomers. Nature404:565[CrossRef]
    [Google Scholar]
  20. Shai Y, Oren Z. 2001; From ‘carpet’ mechanism to de-novo designed diastereomeric cell-selective antimicrobial peptides. Peptides22:1629–1641[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 Chemother41:1738–1742
    [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 Chem46:1567–1570[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 Devine D. A., Hancock R. E. W.. Cambridge: Cambridge University Press;
    [Google Scholar]
  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 A99:5110–5114[CrossRef]
    [Google Scholar]
  25. Toke O. 2005; Antimicrobial peptides: new candidates in the fight against bacterial infections. Biopolymers80:717–735[CrossRef]
    [Google Scholar]
  26. Walsh C. 2003; Antibiotics: Actions, Origins, Resistance Washington, DC: American Society for Microbiology;
    [Google Scholar]
  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 . Biochemistry38:7235–7242[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 Chemother46:3883–3891[CrossRef]
    [Google Scholar]
  29. Yount N. Y, Yeaman M. R. 2005; Multidimensional signatures in antimicrobial peptides. Proc Natl Acad Sci U S A101:7363–7368
    [Google Scholar]
  30. Zasloff M. 2002; Antimicrobial peptides of multicellular organisms. Nature415:389[CrossRef]
    [Google Scholar]
  31. Zhang L, Rozek A, Hancock R. E. 2001; Interaction of cationic antimicrobial peptides with model membranes. J Biol Chem276:35714–35722[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.28812-0
Loading
/content/journal/micro/10.1099/mic.0.28812-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error