Skip to main content
Log in

Synergistic antimicrobial activity of bacteriophages and antibiotics against Staphylococcus aureus

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

Abstract

This study was designed to assess the synergistic antimicrobial effect of phages combined with antibiotics against Staphylococcus aureus. The phage-antibiotic synergy (PAS) effect was evaluated using the fractional inhibitory concentration (FIC) and flow cytometric analysis. The determined minimum inhibitory concentration (MIC) values varied from 0.125 to 128 μg/mL for S. aureus KACC 13236 (SAS) and from 0.25 to >256 μg/mL for S. aureus CCARM 3080 (SAR). The PAS effect was more pronounced in SAS treated with phage SA11 in the presence of cefoxitin (FIC=0.62), chloramphenicol (FIC=0.54), and polymyxin B (FIC=0.38). SAS and SAR cells were injured when exposed to asublethal concentration of ciprofloxacin, whereas these cells were highly susceptible to the phage-antibiotic combined treatment, showing 96% of relative percentages of injured and dead cells. The results suggest that the combined treatment of phages and antibiotics can be used to improve antimicrobial efficacy against antibiotic-resistant bacteria.

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.

Similar content being viewed by others

References

  1. Kaur S, Harjai K, Chhibber S. Methicillin-Resistant Staphylococcus aureus phage plaque size enhancement using sublethal concentrations of antibiotics. Appl. Environ. Microb. 78: 8227–8233 (2012)

    Article  CAS  Google Scholar 

  2. Lowy FD. Staphylococcus aureus infections. New Engl. J. Med. 339: 520–532 (1998)

    Article  CAS  Google Scholar 

  3. Köck R, Becker K, Cookson B, Gemert-Pijnen JEv, Harbarth S, Kluytmans J, Mielke M, Peters G, Skov RL, Struelens MJ, Tacconelli1 E, Torné AN, Witte W, Friedrich AW. Methicillin-resistant Staphylococcus aureus (MRSA): Burden of disease and control challenges in Europe. Euro Surveill 15: 1–9 (2010)

    Google Scholar 

  4. Tice AD, Rehm SJ. Meeting the challenges of methicillin-resistant Staphylococcus aureus with outpatient parenteral antimicrobial therapy. Clin. Infect. Dis. 51: S171–S175 (2010)

    Article  Google Scholar 

  5. Penesyan A, Gillings M, Paulsen I. Antibiotic discovery: Combatting bacterial resistance in cells and in biofilm communities. Molecules 20: 5286–5298 (2015)

    Article  CAS  Google Scholar 

  6. Hede K. Antibiotic resistance: An infectious arms race. Nature 509: S2–S3 (2014)

    Article  Google Scholar 

  7. Yosef I, Manor M, Kiro R, Qimron U. Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria. P. Nat. Acad. Sci. USA 112: 7267–7272 (2015)

    Article  CAS  Google Scholar 

  8. Kaźmierczak Z, Górskiemail A, Dąbrowskaemail K. Facing antibiotic resistance: Staphylococcus aureus phages as a medical tool. Viruses 6: 2551–2570 (2014)

    Article  Google Scholar 

  9. Golkar Z, Bagasra O, Pace DG. Bacteriophage therapy: A potential solution for the antibiotic resistance crisis. J. Infect. Dev. Ctries. 8: 129–236 (2014)

    Article  Google Scholar 

  10. Fischetti VA. Exploiting what phage have evolved to control gram-positive pathogens. Bacteriophage 1: 188–194 (2011)

    Article  Google Scholar 

  11. Vandamme EJ. Phage therapy and phage control: To be revisited urgently!! J. Chem. Tech. Biot. 89: 329–333 (2014)

    Article  CAS  Google Scholar 

  12. Burrowes B, Harper DR, Anderson J, McConville M, Enright MC. Bacteriophage therapy: potential uses in the control of antibiotic-resistant pathogens. Expert Rev. Anti-Infe. 9: 775–785 (2011)

    Article  Google Scholar 

  13. Kirby AE. Synergistic action of gentamicin and bacteriophage in a continuous culture population of Staphylococcus aureus. PLoS ONE 7: e51017 (2012)

    Article  Google Scholar 

  14. Kamal F, Dennis JJ. Burkholderia cepacia complex phage-antibiotic synergy (PAS): Antibiotics stimulate lytic phage activity. Appl. Environ. Microb. 81: 1132–1138 (2015)

    Article  Google Scholar 

  15. Comeau AM, Tétart F, Trojet SN, Prère M-F, Krisch HM. Phage-antibiotic synergy (PAS): β-Lactam and quinolone antibiotics stimulate virulent phage growth. PLoS ONE 2: e799 (2007)

    Article  Google Scholar 

  16. Knezevic P, Curcin S, Aleksic V, Petrusic M, Vlaski L. Phage-antibiotic synergism: A possible approach to combatting Pseudomonas aeruginosa. Res. Microbiol. 164: 55–60 (2013)

    Article  CAS  Google Scholar 

  17. Chibeu A, Agius L, Gao A, Sabour PM, Kropinski AM, Balamurugan S. Efficacy of bacteriophage LISTEXTMP100 combined with chemical antimicrobials in reducing Listeria monocytogenes in cooked turkey and roast beef. Int. J. Food Microbiol. 167: 208–214 (2013)

    Article  CAS  Google Scholar 

  18. CLSI. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M07-A8 (2009)

    Google Scholar 

  19. Meletiadis J, Pournaras S, Roilides E, Walsh TJ. Defining fractional inhibitory concentration index cutoffs for additive interactions based on self-drug additive combinations, Monte Carlo simulation analysis, and in vitro-in vivo correlation data for antifungal drug combinations against Aspergillus fumigatus. Antimicrob. Agents Ch. 54: 602–609 (2010)

    Article  CAS  Google Scholar 

  20. Ayyagari A, Gupta S. Detection of antimicrobial resistance in common gramnegative and gram-positive bacteria encountered in infectious diseases-an update. ICMR Bull. 39: 1–20 (2009)

    Google Scholar 

  21. Hirai K, Aoyama H, Irikura T, Iyobe S, Mitsuhashi S. Differences in susceptibility to quinolones of outer membrane mutants of Salmonella typhimurium and Escherichia coli. Antimicrob. Agents Ch. 29: 535–538 (1986)

    Article  CAS  Google Scholar 

  22. Qimron U, Marintcheva B, Tabor S, Richardson CC. Genomewide screens for Escherichia coli genes affecting growth of T7 bacteriophage. P. Nat. Acad. Sci. USA 103: 19039–19044 (2006)

    Article  CAS  Google Scholar 

  23. Coulter L, McLean R, Rohde R, Aron G. Effect of bacteriophage infection in combination with tobramycin on the emergence of resistance in Escherichia coli and Pseudomonas aeruginosa biofilms. Viruses 6: 3778–3786 (2014)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Juhee Ahn.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jo, A., Ding, T. & Ahn, J. Synergistic antimicrobial activity of bacteriophages and antibiotics against Staphylococcus aureus . Food Sci Biotechnol 25, 935–940 (2016). https://doi.org/10.1007/s10068-016-0153-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-016-0153-0

Keywords

Navigation