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.
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References
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)
Lowy FD. Staphylococcus aureus infections. New Engl. J. Med. 339: 520–532 (1998)
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)
Tice AD, Rehm SJ. Meeting the challenges of methicillin-resistant Staphylococcus aureus with outpatient parenteral antimicrobial therapy. Clin. Infect. Dis. 51: S171–S175 (2010)
Penesyan A, Gillings M, Paulsen I. Antibiotic discovery: Combatting bacterial resistance in cells and in biofilm communities. Molecules 20: 5286–5298 (2015)
Hede K. Antibiotic resistance: An infectious arms race. Nature 509: S2–S3 (2014)
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)
Kaźmierczak Z, Górskiemail A, Dąbrowskaemail K. Facing antibiotic resistance: Staphylococcus aureus phages as a medical tool. Viruses 6: 2551–2570 (2014)
Golkar Z, Bagasra O, Pace DG. Bacteriophage therapy: A potential solution for the antibiotic resistance crisis. J. Infect. Dev. Ctries. 8: 129–236 (2014)
Fischetti VA. Exploiting what phage have evolved to control gram-positive pathogens. Bacteriophage 1: 188–194 (2011)
Vandamme EJ. Phage therapy and phage control: To be revisited urgently!! J. Chem. Tech. Biot. 89: 329–333 (2014)
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)
Kirby AE. Synergistic action of gentamicin and bacteriophage in a continuous culture population of Staphylococcus aureus. PLoS ONE 7: e51017 (2012)
Kamal F, Dennis JJ. Burkholderia cepacia complex phage-antibiotic synergy (PAS): Antibiotics stimulate lytic phage activity. Appl. Environ. Microb. 81: 1132–1138 (2015)
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)
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)
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)
CLSI. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M07-A8 (2009)
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)
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)
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)
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)
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)
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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
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DOI: https://doi.org/10.1007/s10068-016-0153-0