AiM  Vol.5 No.6 , June 2015
Bacteriophage Biocontrol Rescues Mice Bacteremic of Clinically Isolated Mastitis from Dairy Cows Associated with Methicillin-Resistant Staphyloccocus aureus
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.

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.
References
[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. (1991) Growing Lambda-Derived Vectors. In: Ausubel, F.M., et al., Eds., Current Protocols in Molecular Biology, Wiley Interscience, New York, 1.12.1-1.12.3.

[21]   Jassim, S.A.A. and Naji, M.A. (2010) In Vitro Evaluation of the Antiviral Activity of an Extract of Date Palm (Phoenix dactylifera L.) Pits on a Pseudomonas Phage. Evidence-Based Complementary and Alternative Medicine, 7, 57-62. http://dx.doi.org/10.1093/ecam/nem160

[22]   Sive, J.I., Baird, P., Jeziorsk, M., Watkins, A., Hoyland, J.A. and Freemont, A.J. (2002) Expression of Chondrocyte Markers by Cells of Normal and Degenerate Intervertebral Discs. Molecular Pathology, 55, 91-97. http://dx.doi.org/10.1136/mp.55.2.91

[23]   Starks, A.M., Schoeb, T.R., Tamplin, M.L., Parveen, S., Doyle, T.J., Bomeisl, P.E., Escudero, G.M. and Gulig, P.A. (2000) Pathogenesis of Infection by Clinical and Environmental Strains of Vibrio vulnificus in Iron-Dextran-Treated Mice. Infection and Immunity, 68, 5785-5793. http://dx.doi.org/10.1128/IAI.68.10.5785-5793.2000

[24]   Hibma, A.M., Jassim, S.A.A. and Griffiths, M.W. (1997) Infection and Removal of L-Forms of Listeria monocytogenes with Bred Bacteriophage. International Journal of Food Microbiology, 34, 197-207. http://dx.doi.org/10.1016/S0168-1605(96)01190-7

[25]   Phillips, I. and Shannon, K. (1993) Importance of Beta-Lactamase Induction. European Journal of Clinical Microbiology and Infectious Diseases, 12, S19-S26. http://dx.doi.org/10.1007/bf02389873

[26]   Chambers, H.F. (1988) Methicillin-Resistant Staphylococci. Clinical Microbiology Reviews, 1, 173-186.

[27]   Skov, R., Smyth, R., Larsen, A.R., Bolmstrom, A., Karlsson, A., Mills, K., Frimodt-Moller, N. and Kahlmeter, G. (2006) Phenotypic Detection of Methicillin Resistance in Staphylococcus aureus by Disk Diffusion Testing and Etest on Mueller-Hinton Agar. Journal of Clinical Microbiology, 44, 4395-4399. http://dx.doi.org/10.1128/JCM.01411-06

[28]   Kanaan, M.H.G. and AL-Shammary, A.H.A. (2013) Detection of Methicillin or Multidrug Resistant Staphylococcus aureus (MRSA) in Locally Produced Raw Milk and Soft Cheese in Baghdad Markets. Iraqi Journal of Veterinary Medicine, 37, 226-231.

[29]   Khudaier, B.Y., Anad, I.T. and Abbas, B.A. (2014) Isolation of Staphylococcus aureus from Buffalo Milk in Basra Governorate and Detection of Their Susceptibility. Basrah Journal of Veterinary Research, 1, 235-245.

[30]   Quinn, P.J., Markey, B.K., Leonard, F.C., Hartigan, P., Fanning, S. and FitzPatrick, E.S. (2011) Veterinary Microbiology and Microbial Disease. 2nd Edition, Wiley-Blackwell, New York, 536.

[31]   Jay, J.M., Loessner, M.J. and Golden, D.A. (2005) Modern Food Microbiology. 7th Edition, Springer Science + Business Media, New York.

[32]   Ackermann, H.W. and DuBow, M.S. (1987) Viruses of Prokaryotes: General Properties of Bacteriophages. Volume 1, CRC Press Inc., Boca Raton, 49-85.

[33]   Dixon, B. (2004) New Dawn for Phage Therapy. Lancet Infectious Diseases, 4, 186. http://dx.doi.org/10.1016/S1473-3099(04)00951-X

[34]   Capparelli, R., Parlato, M., Borriello, G., Salvatore, P. and Iannelli, D. (2007) Experimental Phage Therapy against Staphylococcus aureus in Mice. Antimicrobial Agents and Chemotherapy, 51, 2765-2773. http://dx.doi.org/10.1128/AAC.01513-06

[35]   Nippe, N., Varga, G., Holzinger, D. and Loffler, B. (2011) Subcutaneous Infection with S. aureus in Mice Reveals Association of Resistance with Influx of Neutrophils and Th2 Response. Journal of Investigative Dermatology, 131, 125-132. http://dx.doi.org/10.1038/jid.2010.282

[36]   Clem, A. (2006) Bacteriophage for the Elimination of Methicillin-Resistant Staphylococcus aureus (MRSA) Colonization and Infection. Ph.D. Thesis, University of South Florida, Tampa.

[37]   Kuklin, N.A., Clark, D.J., Secore, S., Cook, J., Cope, L.D., McNeely, T., et al. (2006) A Novel Staphylococcus aureus Vaccine: Iron Surface Determinant B Induces Rapid Antibody Response in Rhesus Macaques and Specific Increased Survival in a Murine S. aureus Sepsis model. Infection and Immunity, 74, 2215-2223. http://dx.doi.org/10.1128/IAI.74.4.2215-2223.2006

[38]   Matsuzaki, S., Yasuda, M., Nishikawa, H., Kuroda, M., Ujihara, T., Shuin, T., et al. (2003) Experimental Protection of Mice against Lethal Staphylococcus aureus Infection by Novel Bacteriophage φMR11. Journal of Infectious Diseases, 187, 613-624. http://dx.doi.org/10.1086/374001

[39]   Wills, Q.F., Kerrigan, C. and Soothill, J.S. (2005) Experimental Bacteriophage Protection against Staphylococcus aureus Abscesses in a Rabbit Model. Antimicrobial Agents and Chemotherapy, 49, 1220-1221. http://dx.doi.org/10.1128/AAC.49.3.1220-1221.2005

[40]   Chhibber, S., Gupta, P. and Kaur, S. (2014) Bacteriophage as Effective Decolonising Agent for Elimination of MRSA from Anterior Nares of BALB/c Mice. BioMedCentral Microbiology, 14, 212. http://dx.doi.org/10.1186/s12866-014-0212-8

[41]   Honeyman, A.L., Friedman, H. and Bendinelli, M. (2001) Staphylococcus aureus Infection and Disease. Kluwer Academic/Plenum Publishers, New York, 342. http://dx.doi.org/10.1007/b111097

[42]   Khatib, R., Johnson, L.B., Sharma, M., Fakih, M.G., Ganga, R. and Riederer, K. (2009) Persistent Staphylococcus aureus Bacteremia: Incidence and Outcome Trends over Time. Scandinavian Journal of Infectious Diseases, 41, 4-9. http://dx.doi.org/10.1080/00365540802441711

[43]   Fournier, B. and Philpott, G.J. (2005) Recognition of Staphylococcus aureus by the Innate Immune System. Clinical Microbiology Reviews, 18, 521-540. http://dx.doi.org/10.1128/CMR.18.3.521-540.2005

[44]   Tsao, S.-M., Hsu, C.-C. and Yin, M.-C. (2006) Methicillin-Resistant Staphylococcus aureus Infection in Diabetic Mice Enhanced Inflammation and Coagulation. Journal of Medical Microbiology, 55, 379-385. http://dx.doi.org/10.1099/jmm.0.46054-0

[45]   Moreilhon, C., Gras, D., Hologne, C., Bajolet, O., Cottrez, F., Magnone, V., Merten, M., Groux, H., Puchelle, E. and Barbry, P. (2005) Live Staphylococcus aureus and Bacterial Soluble Factors Induce Different Transcriptional Responses in Human Airway Cells. Physiological Genomics, 20, 244-255. http://dx.doi.org/10.1152/physiolgenomics.00135.2004

[46]   Liang, X.D. and Ji, Y.D. (2007) Involvement of α5β1-Integrin and TNF-α in Staphylococcus aureus α-Toxin-Induced Death of Epithelial Cells. Cellular Microbiology, 9, 1809-1821. http://dx.doi.org/10.1111/j.1462-5822.2007.00917.x

[47]   Gordon, R.J. and Lowy, F.D. (2008) Pathogenesis of Methicillin-Resistant Staphylococcus aureus Infection. Clinical Infectious Diseases, 46, S350-S359.

[48]   Lowy, F.D. (1998) Staphylococcus aureus Infections. New England Journal of Medicine, 339, 520-532. http://dx.doi.org/10.1056/NEJM199808203390806

[49]   Biswas, B., Adhya, S., Washart, P., Paul, B., Trostel, A.N., Powell, B., Carlton, R. and Merril, C.R. (2002) Bacteriophage Therapy Rescues Mice Bacteremic from a Clinical Isolate of Vancomycin-Resistant Enterococcus faecium. Infection and Immunity, 70, 204-210. http://dx.doi.org/10.1128/IAI.70.1.204-210.2002

[50]   Fernandez, J., Hilliard, J.J., Morrow, B.J., Melton, J.L., Flamm, R.K., Barron, A.M. and Lynch, A.S. (2011) Efficacy of a New Fluoroquinolone, JNJ-Q2, in Murine Models of Staphylococcus aureus and Streptococcus pneumoniae Skin, Respiratory, and Systemic Infections. Antimicrobial Agents and Chemotherapy, 55, 5522-5528. http://dx.doi.org/10.1128/AAC.00471-11

[51]   Feingold, B.J., Silbergeld, E.K., Curriero, F.C., van Cleef, B.A.G.L., Heck, M.E.O.C. and Kluytmans, J.A.J.W. (2012) Livestock Density as Risk Factor for Livestock-Associated Methicillin-Resistant Staphylococcus aureus, the Netherlands. Emerging Infectious Disease, 18, 1841-1849. http://dx.doi.org/10.3201/eid1811.111850

[52]   Shute, J. (2014) Too Much of Good Thing. The Telegraph. http://s.telegraph.co.uk/graphics/projects/antibiotic-resistance/index.html

 
 
Top