1887

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.

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2016-10-18
2020-09-25
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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 Pept2011:175145 [CrossRef][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 [CrossRef]
    [Google Scholar]
  3. An S. Q., Ryan R. P.. 2016; Combating chronic bacterial infections by manipulating cyclic nucleotide-regulated biofilm formation. Future Med Chem8:949–961 [CrossRef][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 Technol5:1591–1595 [CrossRef][PubMed]
    [Google Scholar]
  5. Batoni G., Maisetta G., Esin S.. 2016; Antimicrobial peptides and their interaction with biofilms of medically relevant bacteria. Biochim Biophys Acta1858:1044–1060 [CrossRef][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 Microbiol37:1771–1776[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 Microbiol71:1–20 [CrossRef][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 Med20:159–161 [CrossRef][PubMed]
    [Google Scholar]
  10. Dickschat J. S.. 2010; Quorum sensing and bacterial biofilms. Nat Prod Rep27:343–369 [CrossRef][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 Chemother58:1107–1117 [CrossRef][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 Nutr56:1262–1274 [CrossRef][PubMed]
    [Google Scholar]
  15. Hancock R. E., Sahl H. G.. 2006; Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol24:1551–1557 [CrossRef][PubMed]
    [Google Scholar]
  16. Jeffcoate W. J., Harding K. G.. 2003; Diabetic foot ulcers. Lancet361:1545–1551 [CrossRef][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. MBio6:e02272-14 [CrossRef][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 Infect54:439–445 [CrossRef][PubMed]
    [Google Scholar]
  19. Kaplan J. B.. 2011; Antibiotic-induced biofilm formation. Int J Artif Organs34:737–751 [CrossRef][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 Immun66:1861–1868[PubMed]
    [Google Scholar]
  21. Lewis K.. 2013; Platforms for antibiotic discovery. Nat Rev Drug Discov12:371–387 [CrossRef][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 Dis39:885–910 [CrossRef][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 Infect18:268–281 [CrossRef][PubMed]
    [Google Scholar]
  24. McAuliffe O., Ross R. P., Hill C.. 2001; Lantibiotics: structure, biosynthesis and mode of action. FEMS Microbiol Rev25:285–308 [CrossRef][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 Pract95:153–161 [CrossRef][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 Microbiol63:1055–1065 [CrossRef][PubMed]
    [Google Scholar]
  27. Mohammad H., Thangamani S., Seleem M.. 2015; Antimicrobial peptides and peptidomimetics – potent therapeutic allies for staphylococcal infections. Curr Pharm Des21:2073–2088 [CrossRef][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 Microbiol61:35–43 [CrossRef]
    [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 Sci23:33 [CrossRef]
    [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 Microbiol66:271–278 [CrossRef][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 Chemother57:5572–5579 [CrossRef][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 Immun76:4176–4182 [CrossRef][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 Chemother49:2612–2617 [CrossRef][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 Sci6:275–286
    [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 Metab34:363–369 [CrossRef][PubMed]
    [Google Scholar]
  36. Richard J. L., Sotto A., Lavigne J. P.. 2011; New insights in diabetic foot infection. World J Diabetes2:24–32 [CrossRef][PubMed]
    [Google Scholar]
  37. Roglic G.. 2016; WHO global report on diabetes: a summary. Int J Non-Commun Dis1:3[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 Chem281:1636–1643 [CrossRef][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 Pract75:47–50 [CrossRef][PubMed]
    [Google Scholar]
  40. Stewart P. S., Costerton J. W.. 2001; Antibiotic resistance of bacteria in biofilms. Lancet358:135–138 [CrossRef][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 Des21:67–84 [CrossRef][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 Macromol88:361–372 [CrossRef][PubMed]
    [Google Scholar]
  43. Vuorisalo S., Venermo M., Lepäntalo M.. 2009; Treatment of diabetic foot ulcers. J Cardiovasc Surg50:275–291
    [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 Protoc3:163–175 [CrossRef][PubMed]
    [Google Scholar]
  45. Zasloff M.. 2002; Antimicrobial peptides of multicellular organisms. Nature415:389–395 [CrossRef][PubMed]
    [Google Scholar]
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