Skip to main content

Advertisement

Log in

A novel nitric oxide producing probiotic patch and its antimicrobial efficacy: preparation and in vitro analysis

  • Biotechnological Products and Process Engineering
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Microbial and fungal infections are a significant consideration in the etiology of all wounds. Numerous antimicrobial and antifungal formulations have been developed with varying degrees of efficacy and stability. Here, we report a nitric oxide producing probiotic adhesive patch device and investigate its antimicrobial and antifungal efficacy in vitro. This probiotic patch utilizes the metabolic activity of immobilized lactic acid bacteria, glucose, and nitrite salts for the production of gaseous nitric oxide (gNO), which is used as an antimicrobial agent against bacterial and fungal pathogens. Results show that application of gNO-producing probiotic patches to cultures of E. coli, S. aureus, P. aeruginosa, MRSA, T. mentagrophytes, and T. rubrum resulted in complete cell death at between 4 and 8 h, and application to cultures of A. baumannii, resulted in fewer than ten colonies detected per milliliter at 6 h. These results demonstrate that a gNO-producing probiotic patch device containing bacteria, glucose, and nitrite salts can produce sufficient levels of gNO over a therapeutically relevant duration to kill common bacterial and fungal wound pathogens in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Adams LB, Hibbs JB Jr, Taintor RR, Krahenbuhl JL (1990) Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from l-arginine. J Immunol 144:2725–2729

    CAS  Google Scholar 

  • Anstey NM, Weinberg JB, Hassanali MY, Mwaikambo ED, Manyenga D, Misukonis MA, Arnelle DR, Hollis D, McDonald MI, Granger DL (1996) Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression. J Exp Med 184:557–567

    Article  CAS  Google Scholar 

  • Augusto O, Linares E, Giorgio S (1996) Possible roles of nitric oxide and peroxynitrite in murine leishmaniasis. Braz J Med Biol Res 29:853–862

    CAS  Google Scholar 

  • De Groote MA, Fang FC (1995) NO inhibitions: antimicrobial properties of nitric oxide. Clin Infect Dis 21(Suppl 2):S162–S165

    Google Scholar 

  • Evans TJ, Strivens E, Carpenter A, Cohen J (1993) Differences in cytokine response and induction of nitric oxide synthase in endotoxin-resistant and endotoxin-sensitive mice after intravenous gram-negative infection. J Immunol 150:5033–5040

    CAS  Google Scholar 

  • Fang FC (1997) Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity. J Clin Invest 99:2818–2825

    Article  CAS  Google Scholar 

  • Ghaffari A, Miller CC, McMullin B, Ghahary A (2006) Potential application of gaseous nitric oxide as a topical antimicrobial agent. Nitric Oxide 14:21–29

    Article  CAS  Google Scholar 

  • Hetrick EM, Shin JH, Stasko NA, Johnson CB, Wespe DA, Holmuhamedov E, Schoenfisch MH (2008) Bactericidal efficacy of nitric oxide-releasing silica nanoparticles. ACS Nano 2:235–246

    Article  CAS  Google Scholar 

  • Hetrick EM, Shin JH, Paul HS, Schoenfisch MH (2009) Anti-biofilm efficacy of nitric oxide-releasing silica nanoparticles. Biomaterials 30:2782–2789

    Article  CAS  Google Scholar 

  • Ischiropoulos H, al-Mehdi AB (1995) Peroxynitrite-mediated oxidative protein modifications. FEBS Lett 364:279–282

    Article  CAS  Google Scholar 

  • Juedes MJ, Wogan GN (1996) Peroxynitrite-induced mutation spectra of pSP189 following replication in bacteria and in human cells. Mutat Res 349:51–61

    Google Scholar 

  • Kawanishi M (1995) Nitric oxide inhibits Epstein–Barr virus DNA replication and activation of latent EBV. Intervirology 38:206–213

    CAS  Google Scholar 

  • Morris SL, Hansen JN (1981) Inhibition of Bacillus cereus spore outgrowth by covalent modification of a sulfhydryl group by nitrosothiol and iodoacetate. J Bacteriol 148:465–471

    CAS  Google Scholar 

  • Park SY, Ji GE, Ko YT, Jung HK, Ustunol Z, Pestka JJ (1999) Potentiation of hydrogen peroxide, nitric oxide, and cytokine production in RAW 264.7 macrophage cells exposed to human and commercial isolates of Bifidobacterium. Int J Food Microbiol 46:231–241

    Article  CAS  Google Scholar 

  • Vazquez-Torres A, Jones-Carson J, Balish E (1996) Peroxynitrite contributes to the candidacidal activity of nitric oxide-producing macrophages. Infect Immun 64:3127–3133

    CAS  Google Scholar 

  • Weller R, Price RJ, Ormerod AD, Benjamin N, Leifert C (2001) Antimicrobial effect of acidified nitrite on dermatophyte fungi, Candida and bacterial skin pathogens. J Appl Microbiol 90:648–652

    Article  CAS  Google Scholar 

  • Zeina B, Banfield C, al-Assad S (1997) Topical glyceryl trinitrate: a possible treatment for cutaneous leishmaniasis. Clin Exp Dermatol 22:244–245

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge financial support from the Industrial Research Assistance Program of the National Research Council of Canada (IRAP-NRC) and from Micropharma Limited.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Satya Prakash.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jones, M.L., Ganopolsky, J.G., Labbé, A. et al. A novel nitric oxide producing probiotic patch and its antimicrobial efficacy: preparation and in vitro analysis. Appl Microbiol Biotechnol 87, 509–516 (2010). https://doi.org/10.1007/s00253-010-2490-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-010-2490-x

Keywords

Navigation