Guar gum as a new antimicrobial peptide delivery system against diabetic foot ulcers isolates Free

Abstract

Diabetic patients frequently develop diabetic foot ulcers (DFUs), particularly those patients vulnerable to opportunistic infections. It is urgent to find new treatments for bacterial infections. The antimicrobial peptide (AMP) nisin is a potential candidate, mainly due to its broad spectrum of action against pathogens. Considering that AMP can be degraded or inactivated before reaching its target at therapeutic concentrations, it is mandatory to establish effective AMP delivery systems, with the natural polysaccharide guar gum being one of the most promising. We analysed the antimicrobial potential of nisin against 23 DFU biofilm-producing isolates. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were determined for nisin diluted in HCl and incorporated in guar gum gel. Statistical analysis was performed using the Wilcoxon matched-pair test. Nisin was effective against all isolates, including some multidrug-resistant clinical isolates, independent of whether it is incorporated in guar gum. While differences among MIC, MBC and MBIC values were observed for HCl- and guar gum- nisin, no significant differences were found between MBEC values. Inhibitory activity of both systems seems to differ only twofold, which does not compromise guar gum gel efficiency as a delivery system. Our results highlight the potential of nisin as a substitute for or complementary therapy to current antibiotics used for treating DFU infections, which is extremely relevant considering the increase in multidrug-resistant bacteria dissemination. The guar gum gel represents an alternative, practical and safe delivery system for AMPs, allowing the development of novel topical therapies as treatments for bacterial skin infections.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000329
2016-10-18
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jmm/65/10/1092.html?itemId=/content/journal/jmm/10.1099/jmm.0.000329&mimeType=html&fmt=ahah

References

  1. Abts A., Mavaro A., Stindt J., Bakkes P., Metzger S., Driessen A., Smits S., Schmitt L. 2011; Easy and rapid purification of highly active nisin. Int J Pept 2011:175145 [View Article][PubMed]
    [Google Scholar]
  2. Akhi M. T., Ghotaslou R., Memar M. Y., Asgharzadeh M., Varshochi M., Pirzadeh T., Alizadeh N. 2016; Frequency of MRSA in diabetic foot infections. Int J Diab Dev Ctries1–5 [View Article]
    [Google Scholar]
  3. An S. Q., Ryan R. P. 2016; Combating chronic bacterial infections by manipulating cyclic nucleotide-regulated biofilm formation. Future Med Chem 8:949–961 [View Article][PubMed]
    [Google Scholar]
  4. Armstrong D. G., Cohen K., Courric S., Bharara M., Marston W. 2011; Diabetic foot ulcers and vascular insufficiency: our population has changed, but our methods have not. J Diabetes Sci Technol 5:1591–1595 [View Article][PubMed]
    [Google Scholar]
  5. Batoni G., Maisetta G., Esin S. 2016; Antimicrobial peptides and their interaction with biofilms of medically relevant bacteria. Biochim Biophys Acta 1858:1044–1060 [View Article][PubMed]
    [Google Scholar]
  6. Ceri H., Olson M. E., Stremick C., Read R. R., Morck D., Buret A. 1999; The Calgary biofilm device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol 37:1771–1776[PubMed]
    [Google Scholar]
  7. Cleveland J., Montville T. J., Nes I. F., Chikindas M. L. 2001; Bacteriocins: safe, natural antimicrobials for food preservation. Int J Food Microbiol 71:1–20 [View Article][PubMed]
    [Google Scholar]
  8. CLSI 2013 Performance Standards for Antimicrobial Susceptibility Testing Approved Standard 23rd Informational Supplement M100-S23 Wayne, PA: Clinical and Laboratory Standards Institute
    [Google Scholar]
  9. Dang C. N., Prasad Y. D., Boulton A. J., Jude E. B. 2003; Methicillin-resistant Staphylococcus aureus in the diabetic foot clinic: a worsening problem. Diabet Med 20:159–161 [View Article][PubMed]
    [Google Scholar]
  10. Dickschat J. S. 2010; Quorum sensing and bacterial biofilms. Nat Prod Rep 27:343–369 [View Article][PubMed]
    [Google Scholar]
  11. ECDC 2015 Annual Report of the European Antimicrobial Resistance Surveillance Network Antimicrobial Resistance Surveillance in Europe 2014 Stockholm, Sweden: European Centre for Disease Prevention and Control
    [Google Scholar]
  12. EFSA 2006; The use of nisin (E 234) as a food additive. EFSA Journal 314:1–16
    [Google Scholar]
  13. French G. L. 2006; Bactericidal agents in the treatment of MRSA infections – the potential role of daptomycin. J Antimicrob Chemother 58:1107–1117 [View Article][PubMed]
    [Google Scholar]
  14. Gharsallaoui A., Oulahal N., Joly C., Degraeve P. 2016; Nisin as a food preservative: part 1: physicochemical properties, antimicrobial activity, and main uses. Crit Rev Food Sci Nutr 56:1262–1274 [View Article][PubMed]
    [Google Scholar]
  15. Hancock R. E., Sahl H. G. 2006; Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24:1551–1557 [View Article][PubMed]
    [Google Scholar]
  16. Jeffcoate W. J., Harding K. G. 2003; Diabetic foot ulcers. Lancet 361:1545–1551 [View Article][PubMed]
    [Google Scholar]
  17. Jenkins A., Diep B. A., Mai T. T., Vo N. H., Warrener P., Suzich J., Stover C. K., Sellman B. R. 2015; Differential expression and roles of Staphylococcus aureus virulence determinants during colonization and disease. MBio 6:e02272-14 [View Article][PubMed]
    [Google Scholar]
  18. Kandemir O., Akbay E., Sahin E., Milcan A., Gen R. 2007; Risk factors for infection of the diabetic foot with multi-antibiotic resistant microorganisms. J Infect 54:439–445 [View Article][PubMed]
    [Google Scholar]
  19. Kaplan J. B. 2011; Antibiotic-induced biofilm formation. Int J Artif Organs 34:737–751 [View Article][PubMed]
    [Google Scholar]
  20. Kirikae T., Hirata M., Yamasu H., Kirikae F., Tamura H., Kayama F., Nakatsuka K., Yokochi T., Nakano M. 1998; Protective effects of a human 18-kilodalton cationic antimicrobial protein (CAP18)-derived peptide against murine endotoxemia. Infect Immun 66:1861–1868[PubMed]
    [Google Scholar]
  21. Lewis K. 2013; Platforms for antibiotic discovery. Nat Rev Drug Discov 12:371–387 [View Article][PubMed]
    [Google Scholar]
  22. Lipsky B. A., Berendt A. R., Deery H. G., Embil J. M., Joseph W. S., Karchmer A. W., LeFrock J. L., Lew D. P., Mader J. T. et al. 2004; Diagnosis and treatment of diabetic foot infections. Clin Infect Dis 39:885–910 [View Article][PubMed]
    [Google Scholar]
  23. Magiorakos A. P., Srinivasan A., Carey R. B., Carmeli Y., Falagas M. E., Giske C. G., Harbarth S., Hindler J. F., Kahlmeter G. et al. 2012; Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281 [View Article][PubMed]
    [Google Scholar]
  24. McAuliffe O., Ross R. P., Hill C. 2001; Lantibiotics: structure, biosynthesis and mode of action. FEMS Microbiol Rev 25:285–308 [View Article][PubMed]
    [Google Scholar]
  25. Mendes J. J., Marques-Costa A., Vilela C., Neves J., Candeias N., Cavaco-Silva P., Melo-Cristino J. 2012; Clinical and bacteriological survey of diabetic foot infections in Lisbon. Diabetes Res Clin Pract 95:153–161 [View Article][PubMed]
    [Google Scholar]
  26. Mendes J. J., Leandro C., Mottola C., Barbosa R., Silva F. A., Oliveira M., Vilela C. L., Melo-Cristino J., Górski A. et al. 2014; In vitro design of a novel lytic bacteriophage cocktail with therapeutic potential against organisms causing diabetic foot infections. J Med Microbiol 63:1055–1065 [View Article][PubMed]
    [Google Scholar]
  27. Mohammad H., Thangamani S., Seleem M. 2015; Antimicrobial peptides and peptidomimetics – potent therapeutic allies for staphylococcal infections. Curr Pharm Des 21:2073–2088 [View Article][PubMed]
    [Google Scholar]
  28. Mottola C., Mendes J. J., Cristino J. M., Cavaco-Silva P., Tavares L., Oliveira M. 2016a; Polymicrobial biofilms by diabetic foot clinical isolates. Folia Microbiol 61:35–43 [View Article]
    [Google Scholar]
  29. Mottola C., Semedo-Lemsaddek T., Mendes J. J., Melo-Cristino J., Tavares L., Cavaco-Silva P., Oliveira M. 2016b; Molecular typing, virulence traits and antimicrobial resistance of diabetic foot staphylococci. J Biomed Sci 23:33 [View Article]
    [Google Scholar]
  30. O'Driscoll N. H., Labovitiadi O., Cushnie T. P., Matthews K. H., Mercer D. K., Lamb A. J. 2013; Production and evaluation of an antimicrobial peptide-containing wafer formulation for topical application. Curr Microbiol 66:271–278 [View Article][PubMed]
    [Google Scholar]
  31. Okuda K., Zendo T., Sugimoto S., Iwase T., Tajima A., Yamada S., Sonomoto K., Mizunoe Y. 2013; Effects of bacteriocins on methicillin-resistant Staphylococcus aureus biofilm. Antimicrob Agents Chemother 57:5572–5579 [View Article][PubMed]
    [Google Scholar]
  32. Overhage J., Campisano A., Bains M., Torfs E. C., Rehm B. H., Hancock R. E. 2008; Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun 76:4176–4182 [View Article][PubMed]
    [Google Scholar]
  33. Pettit R. K., Weber C. A., Kean M. J., Hoffmann H., Pettit G. R., Tan R., Franks K. S., Horton M. L. 2005; Microplate Alamar blue assay for Staphylococcus epidermidis biofilm susceptibility testing. Antimicrob Agents Chemother 49:2612–2617 [View Article][PubMed]
    [Google Scholar]
  34. Reddy K., Mohan G. K., Satla S., Gaikwad S. 2011; Natural polysaccharides: versatile excipients for controlled drug delivery systems. Asian J Pharm Sci 6:275–286
    [Google Scholar]
  35. Richard J. L., Sotto A., Jourdan N., Combescure C., Vannereau D., Rodier M., Lavigne J. P. Nîmes University Hospital Working Group on the Diabetic Foot (GP30) 2008; Risk factors and healing impact of multidrug-resistant bacteria in diabetic foot ulcers. Diabetes Metab 34:363–369 [View Article][PubMed]
    [Google Scholar]
  36. Richard J. L., Sotto A., Lavigne J. P. 2011; New insights in diabetic foot infection. World J Diabetes 2:24–32 [View Article][PubMed]
    [Google Scholar]
  37. Roglic G. 2016; WHO global report on diabetes: a summary. Int J Non-Commun Dis 1:3 [CrossRef]
    [Google Scholar]
  38. Rosenfeld Y., Papo N., Shai Y. 2006; Endotoxin (lipopolysaccharide) neutralization by innate immunity host-defense peptides. peptide properties and plausible modes of action. J Biol Chem 281:1636–1643 [View Article][PubMed]
    [Google Scholar]
  39. Stanaway S., Johnson D., Moulik P., Gill G. 2007; Methicillin-resistant Staphylococcus aureus (MRSA) isolation from diabetic foot ulcers correlates with nasal MRSA carriage. Diabetes Res Clin Pract 75:47–50 [View Article][PubMed]
    [Google Scholar]
  40. Stewart P. S., Costerton J. W. 2001; Antibiotic resistance of bacteria in biofilms. Lancet 358:135–138 [View Article][PubMed]
    [Google Scholar]
  41. Strempel N., Strehmel J., Overhage J. 2015; Potential application of antimicrobial peptides in the treatment of bacterial biofilm infections. Curr Pharm Des 21:67–84 [View Article][PubMed]
    [Google Scholar]
  42. Thombare N., Jha U., Mishra S., Siddiqui M. Z. 2016; Guar gum as a promising starting material for diverse applications: a review. Int J Biol Macromol 88:361–372 [View Article][PubMed]
    [Google Scholar]
  43. Vuorisalo S., Venermo M., Lepäntalo M. 2009; Treatment of diabetic foot ulcers. J Cardiovasc Surg 50:275–291
    [Google Scholar]
  44. Wiegand I., Hilpert K., Hancock R. E. 2008; Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 3:163–175 [View Article][PubMed]
    [Google Scholar]
  45. Zasloff M. 2002; Antimicrobial peptides of multicellular organisms. Nature 415:389–395 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000329
Loading
/content/journal/jmm/10.1099/jmm.0.000329
Loading

Data & Media loading...

Most cited Most Cited RSS feed