Bacteriophage Biocontrol Rescues Mice Bacteremic of Clinically Isolated Mastitis from Dairy Cows Associated with Methicillin-Resistant Staphyloccocus aureus
Affiliation(s)
1 Department of Microbiology, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq. 2 Food Pollution Research Centre, Ministry of Science and Technology, Baghdad, Iraq. 3 Applied Bio Research Inc., Windsor, Canada.
1 Department of Microbiology, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq. 2 Food Pollution Research Centre, Ministry of Science and Technology, Baghdad, Iraq. 3 Applied Bio Research Inc., Windsor, Canada.
ABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) is among the most alarming pathogens affecting both humans and the global bovine industry. The current control measures in hospitals and on farms for MRSA have proven to be inadequate leaving a need for new rapid control methods to curb MRSA infections in situ. New control measures for bacterial infection are widely sought, with particular interest in the applications for bacteriophages (phages) as a biocontrol or therapeutic agent. The current study uses a wild highly lytic phage isolated from cow’s milk taken from three farms in Baghdad, Iraq. The resulting phage was able to rescue 100% of the mice from a median lethal dose (LD50) or (1 × 108 CFU mL-1 per mouse) for MRSA wild isolates achieved when the phage: bacteria ratio was 100:1. Even when treatment was delayed for 6 h post lethal infection, to the point where all mice were moribund, 80% of them were rescued by a single injection of this phage preparation. Based on the current results, a comprehensive study is needed to guide further research on the MRSA phage as a biocontrol for MRSA mastitis in dairy cows to replace or reduce the use of antibiotics in animal husbandry.
Methicillin-resistant Staphylococcus aureus (MRSA) is among the most alarming pathogens affecting both humans and the global bovine industry. The current control measures in hospitals and on farms for MRSA have proven to be inadequate leaving a need for new rapid control methods to curb MRSA infections in situ. New control measures for bacterial infection are widely sought, with particular interest in the applications for bacteriophages (phages) as a biocontrol or therapeutic agent. The current study uses a wild highly lytic phage isolated from cow’s milk taken from three farms in Baghdad, Iraq. The resulting phage was able to rescue 100% of the mice from a median lethal dose (LD50) or (1 × 108 CFU mL-1 per mouse) for MRSA wild isolates achieved when the phage: bacteria ratio was 100:1. Even when treatment was delayed for 6 h post lethal infection, to the point where all mice were moribund, 80% of them were rescued by a single injection of this phage preparation. Based on the current results, a comprehensive study is needed to guide further research on the MRSA phage as a biocontrol for MRSA mastitis in dairy cows to replace or reduce the use of antibiotics in animal husbandry.
KEYWORDS
Bacteriophages, Phage, Biocontrol, Methicillin-Resistant Staphyloccocus aureus, MRSA, Mastitis, Antibiotics
Bacteriophages, Phage, Biocontrol, Methicillin-Resistant Staphyloccocus aureus, MRSA, Mastitis, Antibiotics
Cite this paper
Aldoori, A. , Mahdii, E. , Abbas, A. and Jassim, S. (2015) Bacteriophage Biocontrol Rescues Mice Bacteremic of Clinically Isolated Mastitis from Dairy Cows Associated with Methicillin-Resistant Staphyloccocus aureus. Advances in Microbiology, 5, 383-403. doi: 10.4236/aim.2015.56040.
Aldoori, A. , Mahdii, E. , Abbas, A. and Jassim, S. (2015) Bacteriophage Biocontrol Rescues Mice Bacteremic of Clinically Isolated Mastitis from Dairy Cows Associated with Methicillin-Resistant Staphyloccocus aureus. Advances in Microbiology, 5, 383-403. doi: 10.4236/aim.2015.56040.
References
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[1] Barrett, F.F., McGehee, R.F. and Finland, M. (1968) Methicillin Resistant Staphylococcus aureus at Boston City Hospital. Bacteriologic and Epidemiologic Observations. New England Journal of Medicine, 279, 441-448. http://dx.doi.org/10.1056/NEJM196808292790901 [2] Enright, M.C., Robinson, D.A., Randle, G., Feil, E.J., Grundmann, H. and Spratt, B.G. (2002) The Evolutionary History of Methicillin-Resistant Staphylococcus aureus (MRSA). Proceedings of the National Academy of Sciences of the United States of America, 99, 7687-7692. http://dx.doi.org/10.1073/pnas.122108599 [3] Palavecino, E.L. (2014) Clinical, Epidemiologic, and Laboratory Aspects of Methicillin-Resistant Staphylococcus aureus Infections. Methods in Molecular Biology, 1085, 1-24. http://dx.doi.org/10.1007/978-1-62703-664-1_1 [4] CDC—Centers for Disease Control and Prevention (1999) Four Pediatric Deaths from Community-Acquired Methicillin-Resistant Staphylococcus aureus Minnesota and North Dakota, 1997-1999. Morbidity and Mortality Weekly Report, 48, 707-710. [5] Klevens, R.M., Morrison, M.A. and Nadle, J. (2007) Invasive Methicillin-Resistant Staphylococcus aureus Infections in the United States. Journal of the American Medical Association, 2298, 1763-1771. http://dx.doi.org/10.1001/jama.298.15.1763 [6] Diep, B.A. and Otto, M. (2008) The Role of Virulence Determinants in Community-Associated MRSA Pathogenesis. Trends in Microbiology, 16, 361-369. http://dx.doi.org/10.1016/j.tim.2008.05.002 [7] Wendlandt, S., Schwarz, S. and Silley, P. (2013) Methicillin-Resistant Staphylococcus aureus: A Food-Borne Pathogen? Annual Review of Food Science and Technology, 4, 117-1139. http://dx.doi.org/10.1146/annurev-food-030212-182653 [8] HSI—Humane Society International (2013) An HSI Report: Industrial Farm Animal Production and Livestock Associated MRSA (Methicillin Resistant Staphylococcus aureus). http://www.hsi.org/assets/pdfs/hsi-fa-white-papers/ifap_and_mrsa.pdf [9] Kock, R., Schaumburg, F., Mellmann, A., Koksal, M., Jurke, A., Becker, K. and Friedrich, A.W. (2013) Livestock-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) as Causes of Human Infection and Colonization in Germany. PLoS ONE, 8, Article ID: e55040. http://dx.doi.org/10.1371/journal.pone.0055040 [10] Jassim, S.A.A. and Limoges, R.G. (2014) Natural Solution to Antibiotic Resistance: Bacteriophages “The Living Drugs”. World Journal of Microbiology and Biotechnology, 30, 2153-2170. http://dx.doi.org/10.1007/s11274-014-1655-7 [11] Tacconelli, E., De Angelis, G., Cataldo, M.A., Pozzi, E. and Cauda, R. (2008) Does Antibiotic Exposure Increase the Risk of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolation? A Systematic Review and Meta-Analysis. Journal of Antimicrobial Chemotherapy, 61, 26-38. http://dx.doi.org/10.1093/jac/dkm416 [12] Graham, P.L., Lin, S. and Larson, E. (2006) A US Population-Based Survey of Staphylococcus aureus Colonization. Annals of Internal Medicine, 144, 318-325. http://dx.doi.org/10.7326/0003-4819-144-5-200603070-00006 [13] Jassim, S.A.A., Abdulamir, A.S. and Abu Bakar, F. (2012) Novel Phage-Based Bio-Processing of Pathogenic Escherichia coli and Its Biofilms. World Journal of Microbiology and Biotechnology, 28, 47-60. http://dx.doi.org/10.1007/s11274-011-0791-6 [14] Abdulamir, A.S., Jassim, S.A.A. and Abu Bakar, F. (2014) Novel Approach of Using a Cocktail of Designed Bacteriophages against Gut Pathogenic E. coli for Bacterial Load Biocontrol. Annals of Clinical Microbiology and Antimicrobials, 13, 39. http://www.ann-clinmicrob.com/content/pdf/s12941-014-0039-z.pdf http://dx.doi.org/10.1186/s12941-014-0039-z [15] Embleton, M.L., Nair, S.P., Heywood, W., Menon, D.C., Cookson, B.D. and Wilson, M. (2005) Development of a Novel Targeting System for Lethal Photosensitization of Antibiotic-Resistant Strains of Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 49, 3690-3696. http://dx.doi.org/10.1128/AAC.49.9.3690-3696.2005 [16] O’Flaherty, S., Ross, R.P., Meaney, W., Fitzgerald, G.F., Elbreki, M.F. and Coffey, A. (2005) Potential of the Polyvalent Anti-Staphylococcus Bacteriophage K for Control of Antibiotic-Resistant Staphylococci from Hospitals. Applied and Environmental Microbiology, 71, 1836-1842. http://dx.doi.org/10.1128/AEM.71.4.1836-1842.2005 [17] Rashel, M., Uchiyama, J., Ujihara, T., Uehara, Y., Kuramoto, S., Sugihara, S., Yagyu, K., Muraoka, A., Sugai, M., Hiramatsu, K., Honke, K. and Matsuzaki, S. (2007) Efficient Elimination of Multidrug-Resistant Staphylococcus aureus by Cloned Lysin Derived from Bacteriophage φMR11. Journal of Infectious Diseases, 196, 1237-1247. http://dx.doi.org/10.1086/521305 [18] Whyte, D., Walmsley, M., Liew, A., Claycomb, R. and Mein, G. (2005) Chemical and Rheological Aspects of Gel Formation in the California Mastitis Test. Journal of Dairy Research, 72, 115-121. http://dx.doi.org/10.1017/S0022029904000561 [19] De Neeling, A.J., Van Leeuwen, W.J., Schouls, L.M., Schot, C.S., Van Veen-Rutgers, A., Beunders, A.J., Buiting, A.G., Hol, C., Ligtvoet, E.E., Petit, P.L., Sabbe, L.J., Van Griethuysen, A.J. and Van Embden, J.D. (1998) Resistance of Staphylococci in the Netherlands: Surveillance by an Electronic Network during 1989-1995. Journal of Antimicrobial Chemotherapy, 41, 93-101. http://dx.doi.org/10.1093/jac/41.1.93 [20] Ausubel, F.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Smith, J.A. and Struhl, K. 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