Skip to main content
Food Science and Biotechnology logoLink to Food Science and Biotechnology
. 2016 Aug 31;25(4):1211–1215. doi: 10.1007/s10068-016-0192-6

Role of phage-antibiotic combination in reducing antibiotic resistance in Staphylococcus aureus

Ara Jo 1, Jeongjin Kim 1, Tian Ding 2, Juhee Ahn 1,
PMCID: PMC6049123  PMID: 30263396

Abstract

This study was designed to evaluate the effect of phage-antibiotic synergy in reducing antibiotic resistance. The initial numbers of Staphylococcus aureus treated with ciprofloxacin, phages, and combination were significantly reduced by 3.47, 4.62, and 5.75 log CFU/mL, respectively, at the early 12 h of incubation. The combination treatment most effectively inhibited the growth of S. aureus, showing more than 4 log reduction in 18 h of incubation at 37°C. The significant reduction in biofilm formation by S. aureus was observed at the combination treatment (3.91 log). Ciprofloxacin-treated S. aureus cells became resistant to both ciprofloxacin and phage, showing the mutant frequencies of 27% and 25%, respectively, whereas no antibiotic- and phage-resistant S. aureus cells were observed at the combined treatment of ciprofloxacin and phages. These results provide useful information for reducing the risk of antibiotic resistance in human and food animals.

Keywords: phage-antibiotic combination, ciprofloxacin, Staphylococcus aureus, antibiotic resistance, mutant frequency

References

  • 1.Sergelidis D, Papadopoulos T, Komodromos D, Sergelidou E, Lazou T, Papagianni M, Zdragas A, Papa A. Isolation of methicillin-resistant Staphylococcus aureus from small ruminants and their meat at slaughter and retail level in Greece. Lett. Appl. Microbiol. 2015;61:498–503. doi: 10.1111/lam.12485. [DOI] [PubMed] [Google Scholar]
  • 2.Hanberger H, Walther S, Leone M, Barie PS, Rello J, Lipman J, Marshall JC, Anzueto A, Sakr Y, Pickkers P, Felleiter P, Engoren M, Vincent J-L. Increased mortality associated with meticillin-resistant Staphylococcus aureus (MRSA) inf ection in t he I ntensive C are Unit: R esults from the EPIC I I study. Int. J. Antimicrob. Ag. 2011;38:331–335. doi: 10.1016/j.ijantimicag.2011.05.013. [DOI] [PubMed] [Google Scholar]
  • 3.Haaber J, Cohn MT, Frees D, Andersen TJ, Ingmer H. Planktonic aggregates of Staphylococcus aureus protect against common antibiotics. PLoS ONE. 2012;7:41075. doi: 10.1371/journal.pone.0041075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Penesyan A, Gillings M, Paulsen I. Antibiotic discovery: Combatting bacterial resistance in cells and in biofilm communities. Molecules. 2015;20:5286–5298. doi: 10.3390/molecules20045286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Hede K. Antibiotic resistance: An infectious arms race. Nature. 2014;509:S2–S3. doi: 10.1038/509S2a. [DOI] [PubMed] [Google Scholar]
  • 6.Kirby AE. Synergistic action of gentamicin and bacteriophage in a continuous culture population of Staphylococcus aureus. PLoS ONE. 2012;7:51017. doi: 10.1371/journal.pone.0051017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Woo J, Ahn J. Assessment of synergistic combination potential of probiotic and bacteriophage against antibiotic-resistant Staphylococcus aureus exposed to simulated intestinal conditions. Arch. Microbiol. 2014;196:719–727. doi: 10.1007/s00203-014-1013-z. [DOI] [PubMed] [Google Scholar]
  • 8.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. 2014;6:3778–3786. doi: 10.3390/v6103778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Qimron U, Marintcheva B, Tabor S, Richardson CC. Genomewide screens for Escherichia coli genes affecting growth of T7 bacteriophage. P. Natl. Acad. Sci. USA. 2006;103:19039–19044. doi: 10.1073/pnas.0609428103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Labrie SJ, Samson JE, Moineau S. Bacteriophage resistance mechanisms. Nat. Rev. Microbiol. 2010;8:317–327. doi: 10.1038/nrmicro2315. [DOI] [PubMed] [Google Scholar]
  • 11.Partridge SR. Analysis of antibiotic resistance regions in Gram-negative bacteria. FEMS Microbiol. Rev. 2011;35:820–855. doi: 10.1111/j.1574-6976.2011.00277.x. [DOI] [PubMed] [Google Scholar]
  • 12.CLSI. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 2009. [Google Scholar]
  • 13.Freeman DJ, Falkiner FR, Keane CT. New method for detecting slime production by coagulase negative staphylococci. J. Clin. Pathol. 1989;42:872–874. doi: 10.1136/jcp.42.8.872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Comeau AM, Tétart F, Trojet SN, Prère M-F, Krisch HM. Phage-antibiotic synergy (PAS): ß-Lactam and quinolone antibiotics stimulate virulent phage growth. PLoS ONE. 2007;2:799. doi: 10.1371/journal.pone.0000799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Tanji Y, Shimada T, Yoichi M, Miyanaga K, Hori K, Unno H. Toward rational control of Escherichia coli O157:H7 by a phage cocktail. Appl. Microbiol. Biot. 2004;64:270–274. doi: 10.1007/s00253-003-1438-9. [DOI] [PubMed] [Google Scholar]
  • 16.Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. Int. J. Antimicrob. Ag. 2010;35:322–332. doi: 10.1016/j.ijantimicag.2009.12.011. [DOI] [PubMed] [Google Scholar]
  • 17.Ahn J, Kim S, Jung L-S, Biswas D. In vitro assessment of the susceptibility of planktonic and attached cells of foodborne pathogens to bacteriophage P22-mediated Salmonella lysates. J. Food Protect. 2013;76:2057–2062. doi: 10.4315/0362-028X.JFP-13-183. [DOI] [PubMed] [Google Scholar]
  • 18.Ryan EM, Alkawareek MY, Donnelly RF, Gilmore BF. Synergistic phageantibiotic combinations for the control of Escherichia coli biofilms in vitro. FEMS Immunol. Med. Mic. 2012;65:395–398. doi: 10.1111/j.1574-695X.2012.00977.x. [DOI] [PubMed] [Google Scholar]
  • 19.Pourmand MR, Abdossamadi Z, Salari MH, Hosseini M. Slime layer formation and the prevalence of mecA and aap genes in Staphylococcus epidermidis isolates. J. Infect. Dev. Ctries. 2011;5:34–40. doi: 10.3855/jidc.984. [DOI] [PubMed] [Google Scholar]
  • 20.Stewart PS, William CJ. Antibiotic resistance of bacteria in biofilms. The Lancet. 2001;358:135–138. doi: 10.1016/S0140-6736(01)05321-1. [DOI] [PubMed] [Google Scholar]
  • 21.Fung-Tomc J, Kolek B, Bonner DP. Ciprofloxacin-induced, low-level resistance to structurally unrelated antibiotics in Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Ch. 1993;37:1289–1296. doi: 10.1128/AAC.37.6.1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Campion JJ, McNamara PJ, Evans ME. Evolution of ciprofloxacin-resistant Staphylococcus aureus in in vitro pharmacokinetic environments. Antimicrob. Agents. Ch. 2004;48:4733–4744. doi: 10.1128/AAC.48.12.4733-4744.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Mizoguchi K, Morita M, Fischer CR, Yoichi M, Tanji Y, Unno H. Coevolution of bacteriophage PP01 and Escherichia coli O157:H7 in continuous culture. Appl. Environ. Microb. 2003;69:170–176. doi: 10.1128/AEM.69.1.170-176.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Food Science and Biotechnology are provided here courtesy of Springer

RESOURCES