1887

Abstract

Antimicrobial peptides are known as immunomodulators and antibiotic enhancers. We report that administration of an antimicrobial peptide, IB-367, was efficacious in increasing the antimicrobial activity of daptomycin and teicoplanin in a mouse model of wound infection caused by meticillin-resistant (MRSA). Mice were assigned to seven groups: an IB-367 pre-treated group with no antibiotics given after challenge, two IB-367 pre-treated groups plus daptomycin or teicoplanin given after challenge, two groups treated with daptomycin or teicoplanin only after challenge, and two control groups without infection or that did not receive any treatment. The main outcome measures were quantitative bacterial culture and analysis of natural killer (NK) cytotoxicity and leukocyte phenotype. The wound, established through the panniculus carnosus muscle of mice, was infected by MRSA. Bacterial cultures of mice receiving antibiotics alone showed a −2 log decrease, whilst those for IB-367 plus daptomycin or teicoplanin showed a −4 log decrease. IB-367 plus daptomycin showed the highest efficacy. The higher antimicrobial effect exerted by IB-367 was associated with increased levels of NK cytotoxicity but not of NK cell number. IB-367 increased the number of both CD11b and Gr-1 cells 3 days after MRSA challenge, whereas both of these leukocyte populations were reduced at 10 days after challenge. Our data suggest that a combination of IB-367 with antibiotic exerts a therapeutic effect and may be useful for the management of staphylococcal wounds.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.057414-0
2013-10-01
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/jmm/62/10/1552.html?itemId=/content/journal/jmm/10.1099/jmm.0.057414-0&mimeType=html&fmt=ahah

References

  1. Allaker R. P. 2008; Host defence peptides-a bridge between the innate and adaptive immune responses. Trans R Soc Trop Med Hyg 102:3–4 [View Article][PubMed]
    [Google Scholar]
  2. Auvynet C., Rosenstein Y. 2009; Multifunctional host defense peptides: antimicrobial peptides, the small yet big players in innate and adaptive immunity. FEBS J 276:6497–6508 [View Article][PubMed]
    [Google Scholar]
  3. Babizhayev M. A. 2010; New concept in nutrition for the maintenance of the aging eye redox regulation and therapeutic treatment of cataract disease; synergism of natural antioxidant imidazole-containing amino acid-based compounds, chaperone, and glutathione boosting agents: a systemic perspective on aging and longevity emerged from studies in humans. Am J Ther 17:373–389[PubMed]
    [Google Scholar]
  4. Boman H. G. 2003; Antibacterial peptides: basic facts and emerging concepts. J Intern Med 254:197–215 [View Article][PubMed]
    [Google Scholar]
  5. Bowdish D. M., Davidson D. J., Scott M. G., Hancock R. E. W. 2005; Immunomodulatory activities of small host defense peptides. Antimicrob Agents Chemother 49:1727–1732 [View Article][PubMed]
    [Google Scholar]
  6. Breen J. O. 2010; Skin and soft tissue infections in immunocompetent patients. Am Fam Physician 81:893–899[PubMed]
    [Google Scholar]
  7. Carretero M., Escámez M. J., García M., Duarte B., Holguín A., Retamosa L., Jorcano J. L., Río M. D., Larcher F. 2008; In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J Invest Dermatol 128:223–236 [View Article][PubMed]
    [Google Scholar]
  8. Cenci E., Pericolini E., Mencacci A., Conti S., Magliani W., Bistoni F., Polonelli L., Vecchiarelli A. 2006; Modulation of phenotype and function of dendritic cells by a therapeutic synthetic killer peptide. J Leukoc Biol 79:40–45 [View Article][PubMed]
    [Google Scholar]
  9. Chen Q., Wade D., Kurosaka K., Wang Z. Y., Oppenheim J. J., Yang D. 2004; Temporin A and related frog antimicrobial peptides use formyl peptide receptor-like 1 as a receptor to chemoattract phagocytes. J Immunol 173:2652–2659[PubMed] [CrossRef]
    [Google Scholar]
  10. Cho Y., Turner J. S., Dinh N. N., Lehrer R. I. 1998; Activity of protegrins against yeast-phase Candida albicans . Infect Immun 66:2486–2493[PubMed]
    [Google Scholar]
  11. CLSI 2003; Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. Approved standard M7–A6. Wayne, PA: Clinical and Laboratory Standards Institute;
    [Google Scholar]
  12. De la Fuente M., Victor V. M. 2000; Anti-oxidants as modulators of immune function. Immunol Cell Biol 78:49–54 [View Article][PubMed]
    [Google Scholar]
  13. De Smet K., Contreras R. 2005; Human antimicrobial peptides: defensins, cathelicidins and histatins. Biotechnol Lett 27:1337–1347 [View Article][PubMed]
    [Google Scholar]
  14. Eliopoulos G. M. 2009; Microbiology of drugs for treating multiply drug-resistant Gram-positive bacteria. J Infect 59:Suppl. 1S17–S24 [View Article][PubMed]
    [Google Scholar]
  15. Enoch S., Harding K. G. 2003; Science behind the removal of barriers to healing. Wounds 15:213–229
    [Google Scholar]
  16. Fields G. B., Noble R. L. 1990; Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Protein Res 35:161–214 [View Article][PubMed]
    [Google Scholar]
  17. Giacometti A., Cirioni O., Ghiselli R., Mocchegiani F., D’Amato G., Del Prete M. S., Orlando F., Kamysz W., Łukasiak J. other authors 2003; Administration of protegrin peptide IB-367 to prevent endotoxin induced mortality in bile duct ligated rats. Gut 52:874–878 [View Article][PubMed]
    [Google Scholar]
  18. Hancock R. E. W. 2001; Cationic peptides: effectors in innate immunity and novel antimicrobials. Lancet Infect Dis 1:156–164 [View Article][PubMed]
    [Google Scholar]
  19. Hancock R. E. W., Scott M. G. 2000; The role of antimicrobial peptides in animal defenses. Proc Natl Acad Sci U S A 97:8856–8861 [View Article][PubMed]
    [Google Scholar]
  20. Ippolito G., Leone S., Lauria F. N., Nicastri E., Wenzel R. P. 2010; Methicillin-resistant Staphylococcus aureus: the superbug. Int J Infect Dis 14:Suppl 4S7–S11 [View Article][PubMed]
    [Google Scholar]
  21. Kaminogawa S., Nanno M. 2004; Modulation of immune functions by foods. Evid Based Complement Alternat Med 1:241–250 [View Article][PubMed]
    [Google Scholar]
  22. Koczulla R., von Degenfeld G., Kupatt C., Krötz F., Zahler S., Gloe T., Issbrücker K., Unterberger P., Zaiou M. other authors 2003; An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111:1665–1672[PubMed] [CrossRef]
    [Google Scholar]
  23. Lowy F. D. 2003; Antimicrobial resistance: the example of Staphylococcus aureus . J Clin Invest 111:1265–1273[PubMed] [CrossRef]
    [Google Scholar]
  24. Messina C., Kirkpatrick D., Fitzgerald P. A., O’Reilly R. J., Siegal F. P., Cunningham-Rundles C., Blaese M., Oleske J., Pahwa S., Lopez C. 1986; Natural killer cell function and interferon generation in patients with primary immunodeficiencies. Clin Immunol Immunopathol 39:394–404 [View Article][PubMed]
    [Google Scholar]
  25. Mookherjee N., Hancock R. E. 2007; Cationic host defence peptides: innate immune regulatory peptides as a novel approach for treating infections. Cell Mol Life Sci 64:922–933 [View Article][PubMed]
    [Google Scholar]
  26. Pace J. L., Yang G. 2006; Glycopeptides: update on an old successful antibiotic class. Biochem Pharmacol 71:968–980 [View Article][PubMed]
    [Google Scholar]
  27. Pertinhez T. A., Conti S., Ferrari E., Magliani W., Spisni A., Polonelli L. 2009; Reversible self-assembly: a key feature for a new class of autodelivering therapeutic peptides. Mol Pharm 6:1036–1039 [View Article][PubMed]
    [Google Scholar]
  28. Pirofski L. A., Casadevall A. 2006; Immunomodulators as an antimicrobial tool. Curr Opin Microbiol 9:489–495 [View Article][PubMed]
    [Google Scholar]
  29. Provinciali M., Di Stefano G., Fabris N. 1992; Optimization of cytotoxic assay by target cell retention of the fluorescent dye carboxyfluorescein diacetate (CFDA) and comparison with conventional 51CR release assay. J Immunol Methods 155:19–24 [View Article][PubMed]
    [Google Scholar]
  30. Provinciali M., Cirioni O., Orlando F., Pierpaoli E., Barucca A., Silvestri C., Ghiselli R., Scalise A., Brescini L. other authors 2011; Vitamin E improves the in vivo efficacy of tigecycline and daptomycin in an animal model of wounds infected with meticillin-resistant Staphylococcus aureus . J Med Microbiol 60:1806–1812 [View Article][PubMed]
    [Google Scholar]
  31. Raad I., Alrahwan A., Rolston K. 1998; Staphylococcus epidermidis: emerging resistance and need for alternative agents. Clin Infect Dis 26:1182–1187 [View Article][PubMed]
    [Google Scholar]
  32. Salzet M. 2002; Antimicrobial peptides are signaling molecules. Trends Immunol 23:283–284 [View Article][PubMed]
    [Google Scholar]
  33. Simonetti O., Cirioni O., Goteri G., Ghiselli R., Silvestri C., Orlando F., Scalise A., Saba V., Scalise G. other authors 2008; Temporin A is effective in the MRSA infected wounds in mice through bactericidial activity and acceleration of wound repair in a murine model. Peptides 29:520–528 [View Article][PubMed]
    [Google Scholar]
  34. Steenbergen J. N., Alder J., Thorne G. M., Tally F. P. 2005; Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections. J Antimicrob Chemother 55:283–288 [View Article][PubMed]
    [Google Scholar]
  35. Stevens D. L. 2009; Treatments for skin and soft-tissue and surgical site infections due to MDR Gram-positive bacteria. J Infect 59:Suppl 1S32–S39 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.057414-0
Loading
/content/journal/jmm/10.1099/jmm.0.057414-0
Loading

Data & Media loading...

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