Skip to main content
SpringerLink
Log in

Safety of using Escherichia coli bacteriophages as a sanitizing agent based on inflammatory responses in rats

  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

Use of bacteriophages as sanitizing agents has received much attention. However, safety in humans is debatable. To determine inflammatory immune responses against bacteriophages, rats were treated with a 8 log plaque-forming cocktail of 5 bacteriophages for pathogenic Escherichia coli per day for 4 weeks. Food consumption, feeding efficiency, and body weight of rats treated with the cocktail were not different from controls. Phages were not detected in the sera of phage-fed rats with no changes in organ weights. Notable changes were not observed upon histopathological examination of the liver, kidney, and spleen. Pro-inflammatory cytokine mRNA expression, except COX-2 (2.4x increase), remained unaffected after treatment with the phage cocktail. No remarkable changes were observed for levels of 12 pro-inflammatory cytokines in sera. Inflammatory responses in rats orally treated with a phage cocktail were not observed. Bacteriophages for E. coli are indicated as immunologically safe in rats.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Merril CR, Scholl D, Adhya SL. The prospect for bacteriophage therapy in western medicine. Nat. Rev. Drug Discov. 2: 489–497 (2003)

    Article  CAS  Google Scholar 

  2. Summers WC. Bacteriophage therapy. Annu. Rev. Microbiol. 55: 437–451 (2001)

    Article  CAS  Google Scholar 

  3. Ackermann HW. Classification of bacteriophages. pp. 8–16. In: The Bacteriophages. 2nd ed. Richard Calendar (ed). Oxford University Press, Oxford, UK (2006)

    Google Scholar 

  4. Bebeacua C, Lai L, Vegge CS, Brøndsted L, Heel M, Veesler D, Cambillau C. Visualizing a complete member by single-particle electron microscopy: The structure of lactococcal phage TP901-1. J. Virol. 87: 1061–1068 (2013)

    Article  CAS  Google Scholar 

  5. Ackermann HW. Phage classification and characterization. pp. 127–140. In: Bacteriophages, Methods in Molecular Biology. 3rd ed. Clokie MRL, Kropinski AM (eds). Humana Press, New York City, NY, USA (2009)

    Google Scholar 

  6. Abdul-Raouf UM, Beuchat LR, Ammar MS. Survival and growth of Escherichia coli O157:H7 in ground, roasted beef as affected by pH, acidulants, and temperature. Appl. Environ. Microbiol. 59: 3464–2368 (1993)

    Google Scholar 

  7. Cho DI. Construction of an antibacterial yeast that producing bacteriocin subpeptin JM4-A or subpeptin JM4-B. PhD Thesis, Konkuk University, Seoul, Korea (2001)

    Google Scholar 

  8. Edrington TS, Callaway TR, Anderson RC, Genovese KJ, Jung YS, McReynolds JL, Bischoff KM, Nisbet DJ. Reduction of E. coli O157:H7 populations in sheep by supplementation of an experimental sodium chlorate product. Small Ruminant Res. 49: 173–181 (2003)

    Article  Google Scholar 

  9. Clark JR, March JB. Bacteriophages and biotechnology: Vaccines, gene therapy, and antibacterials. Trends Biotechnol. 24: 212–218 (2006)

    Article  CAS  Google Scholar 

  10. Chibani-Chennoufi S, Sidoti J, Bruttin A, Kutter E, Sarker S, Brüssow H. In vitro and in vivo bacteriolytic activities of Escherichia coli phages: Implications for phage therapy. Antimicrob. Agents Ch. 48: 2558–2569 (2004)

    Article  CAS  Google Scholar 

  11. Weiss M, Denou E, Bruttin A, Serra-Moreno R, Dillmann ML, Brüssow H. In vivo replication of T4 and T7 bacteriophages in germ-free mice colonized with Escherichia coli. Virolog. 393: 16–23 (2009)

    Article  CAS  Google Scholar 

  12. Bozza FA, Salluh JI, Japiassu AM, Soares M, Assis EF, Gomes RN, Bozza MT, Castro-Faria-Neto HC, Bozza PT. Cytokine profiles as markers of disease severity in sepsis: A multiplex analysis. Crit. Car. 11: R49–R53 (2007)

    Article  Google Scholar 

  13. Brüssow H. Phage therapy: The Escherichia coli experience. Microbiolog. 151: 2133–2140 (2005)

    Google Scholar 

  14. Thiel K. Old dogma, new tricks-21st Century phage therapy. Nat. Biotechnol. 22: 31–36 (2004)

    Article  CAS  Google Scholar 

  15. Hudson JA, Billington C, Carey-Smith G, Greening G. Bacteriophages as biocontrol agents in food. J. Food Protect. 68: 426–437 (2005)

    CAS  Google Scholar 

  16. Garcia P, Rodriguez L, Rodriguez A, Martinez B. Food biopreservation: Promising strategies using bacteriocins, bacteriophages, and endolysins. Trends Food Sci. Tech. 21: 373–382 (2010)

    Article  CAS  Google Scholar 

  17. Modi R, Hirvi Y, Hill A, Griffiths MW. Effect of phage on survival of Salmonella enteritidis during manufacture and storage of Cheddar cheese made from raw and pasteurized milk. J. Food Protect. 64: 927–933 (2001)

    CAS  Google Scholar 

  18. Lu TK, Koeris MS. The next generation of bacteriophage therapy. Curr. Opin. Microbiol. 14: 524–531 (2011)

    Article  Google Scholar 

  19. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am. J. Physiol. Lung Cell Mol. Physiol. 279: 1005–1028 (2000)

    Google Scholar 

  20. Miernikiewicz P, Dabrowska K, Piotrowicz A, Owczarek B, Wojas-Turek J, Kicieliñska J, Rossowska J, Pajtasz-Piasecka E, Hodyra K, Macegoniuk K, Rzewucka K, Kopciuch A, Majka T, Letarov A, Kulikov E, Maciejewski H, Górski A. T4 phage and its head surface proteins do not stimulate inflammatory mediator production. PLoS ONE. 8: e71036 (2013)

    Article  CAS  Google Scholar 

  21. Weber-Dabrowska B, Zimecki M, Mulczyk M. Effective phage therapy is associated with normalization of cytokine production by blood cell cultures. Arch. Immunol. Ther. Ex. 48: 31–37 (2000)

    CAS  Google Scholar 

  22. Dabrowska K, Switala-Jelen K, Opolski A, Weber-Dabrowska B, Gorski A. Bacteriophage penetration in vertebrates. J. Appl. Microbiol. 98: 7–13 (2005)

    Article  CAS  Google Scholar 

  23. Park K, Cha KE, Myung H. Observation of inflammatory responses in mice orally fed with bacteriophage T7. J. Appl. Microbiol. 117: 627–633 (2014)

    Article  CAS  Google Scholar 

  24. Bull JJ, Otto G, Molineux IJ. In vivo growth rates are poorly correlated with phage therapy success in a mouse infection model. Antimicrob. Agents Ch. 56: 949–954 (2012)

    Article  CAS  Google Scholar 

  25. Maura D, Morello E, du Merle L, Bomme P, Le Bouguenec C, Debarbieux L. Intestinal colonization by enteroaggregative Escherichia coli supports longterm bacteriophage replication in mice. Environ. Microbiol. 14: 1844–1854 (2012)

    Article  CAS  Google Scholar 

  26. Zhang W, Mi Z, Yin X, Fan H, An X, Zhang Z, Chen J, Tong Y. Characterization of Enterococcus faecalis phage IME-EF1 and its endolysin. PLoS ON. 8: e80435 (2013)

    Article  Google Scholar 

  27. Kim EJ. Characterization and infection receptor analysis of bacteriophages for Escherichia coli O157:H7 and non-O157 shiga toxin-producing E. coli. MS Thesis, Gachon Universty, Seongnam, Korea (2015)

    Google Scholar 

  28. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using realtime quantitative PCR and the 2(-Delta Delta C(T)) method. Method. 25: 402–408 (2001)

    Article  CAS  Google Scholar 

  29. Denou E, Bruttin A, Barretto C, Ngom-Bru C, Brüssow H, Zuber S. T4 phages against Escherichia coli diarrhea: Potential and problems. Virolog. 388: 21–30 (2009)

    Article  CAS  Google Scholar 

  30. Smolinski AT, Pestka JJ. Comparative effects of the herbal constituent parthenolide (feverfew) on the lipopolysaccharide-induced inflammatory gene expression in murine spleen and liver. J. Inflamm. 2: 6–13 (2005)

    Article  Google Scholar 

  31. Hedi H, Norbert G. Inhibition of IL-6, TNF-α, and cyclooxygenase-2 protein expression by prostaglandin E2-induced IL-10 in bone marrow-derived dendritic cells. Cell Immunol. 228: 99–109 (2004)

    Article  CAS  Google Scholar 

  32. Takemura-Uchiyama I, Uchiyama J, Osanai M, Morimoto N, Asagiri T, Ujihara, T, Daibata M, Sugiura T, Matsuzaki S. Experimental phage therapy against lethal lung-derived septicemia caused by Staphylococcus aureus in mice. Microbes Infect. 16: 512–517 (2014)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Food Science and Biotechnology, Gachon University, Seongnam, Gyeonggi, 13120, Korea

    Ji-Yeon Hwang & Jong-Hyun Park

  2. Department of Life Science, Gachon University, Seongnam, Gyeonggi, 13120, Korea

    Jung-Eun Kim & Yoon-Jae Song

Authors
  1. Ji-Yeon Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jung-Eun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoon-Jae Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jong-Hyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jong-Hyun Park.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hwang, JY., Kim, JE., Song, YJ. et al. Safety of using Escherichia coli bacteriophages as a sanitizing agent based on inflammatory responses in rats. Food Sci Biotechnol 25, 355–360 (2016). https://doi.org/10.1007/s10068-016-0050-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-016-0050-6

Keywords

Search

Navigation