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Bacteriophages for prophylaxis and therapy in cattle, poultry and pigs

  • R. P. Johnson (a1), C. L. Gyles (a2), W. E. Huff (a3), S. Ojha (a1), G. R. Huff (a3), N. C. Rath (a3) and A. M. Donoghue (a3)...

The successful use of virulent (lytic) bacteriophages (phages) in preventing and treating neonatal enterotoxigenic Escherichia coli infections in calves, lambs and pigs has prompted investigation of other applications of phage therapy in food animals. While results have been very variable, some indicate that phage therapy is potentially useful in virulent Salmonella and E. coli infections in chickens, calves and pigs, and in control of the food-borne pathogens Salmonella and Campylobacter jejuni in chickens and E. coli O157:H7 in cattle. However, more rigorous and comprehensive research is required to determine the true potential of phage therapy. Particular challenges include the selection and characterization of phages, practical modes of administration, and development of formulations that maintain the viability of phages for administration. Also, meaningful evaluation of phage therapy will require animal studies that closely represent the intended use, and will include thorough investigation of the emergence and characteristics of phage resistant bacteria. As well, effective use will require understanding the ecology and dynamics of the endemic and therapeutic phages and their interactions with target bacteria in the farm environment. In the event that the potential of phage therapy is realized, adoption will depend on its efficacy and complementarity relative to other interventions. Another potential challenge will be regulatory approval.

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Andreatti Filho RL, Higgins JP, Higgins SE, Gaona G, Wolfenden AD, Tellez G and Hargis BM (2007). Ability of bacteriophages isolated from different sources to reduce Salmonella enterica serovar enteritidis in vitro and in vivo. Poultry Science 86: 19041909.
Atterbury RJ, Dillon E, Swift C, Connerton PL, Frost JA, Dodd CE, Rees CE and Connerton IF (2005). Correlation of Campylobacter bacteriophage with reduced presence of hosts in broiler chicken ceca. Applied and Environmental Microbiology 71: 48854887.
Atterbury RJ, Van Bergen MA, Ortiz F, Lovell MA, Harris JA, De Boer A, Wagenaar JA, Allen VM and Barrow PA (2007). Bacteriophage therapy to reduce Salmonella colonization of broiler chickens. Applied and Environmental Microbiology 73: 45434549.
Bach SJ, McAllister TA, Veira DM, Gannon VPJ and Holly RA (2008). Effect of bacteriophage DC22 on Escherichia coli O157:H7 in an artificial rumen system (Rusitec) and inoculated sheep. Annual Review of Microbiology 52: 89101.
Barnes JH, Vaillancourt JP and Gross WB (2003). Colibacillosis. In: Saif YM (ed.) Diseases of Poultry. Ames, IA: Iowa State University Press, pp. 631656.
Barrow P, Lovell M and Berchieri A (1998). Use of lytic bacteriophage for control of experimental Escherichia coli septicemia and meningitis in chickens and calves. Clinical and Diagnostic Laboratory Immunology 5: 294298.
Barrow PA (2001). The use of bacteriophages for treatment and prevention of bacterial disease in animals and animal models of human infection. Journal of Chemical Technology and Biotechnology 76: 677682.
Berchieri A Jr, Lovell MA and Barrow PA (1991). The activity in the chicken alimentary tract of bacteriophages lytic for Salmonella typhimurium. Research in Microbiology 142: 541549.
Besser TE, Hancock DD, Pritchett LC, McRae EM, Rice DH and Tarr PI (1997). Duration of detection of fecal excretion of Escherichia coli O157:H7 in cattle. Journal of Infectious Diseases 175: 726729.
Biswas B, Adhya S, Washart P, Paul B, Trostel AN, Powell B, Carlton R and Merril CR (2002). Bacteriophage therapy rescues mice bacteremic from a clinical isolate of vancomycin-resistant Enterococcus faecium [erratum appears in Infection and Immunity 2002;70(3):1664]. Infection and Immunity 70: 204210.
Boerlin P, Travis R, Gyles CL, Reid-Smith R, Janecko N, Lim H, Nicholson V, McEwen SA, Friendship R and Archambault M (2005). Antimicrobial resistance and virulence genes of Escherichia coli isolates from swine in Ontario. Applied and Environmental Microbiology 71: 67536761.
Brüssow H and Kutter E (2005) Phage Ecology. In: Kutter E and Sulakvelidze A (eds) Bacteriophages Biology and Applications. Boca Raton, FL: CRC Press, pp. 129163.
Callaway TR, Edrington TS, Brabban AD, Anderson RC, Rossman ML, Engler MJ, Carr MA, Genovese KJ, Keen JE, Looper ML, Kutter EM and Nisbet DJ (2008). Bacteriophage isolated from feedlot cattle can reduce Escherichia coli O157:H7 populations in ruminant gastrointestinal tracts. Foodborne Pathogens and Disease 5: 183191.
Carlton RM, Noordman WH, Biswas B, de Meester ED and Loessner MJ (2005). Bacteriophage P100 for control of Listeria monocytogenes in foods: genome sequence, bioinformatic analyses, oral toxicity study, and application. Regulatory Toxicology and Pharmacology 43: 301312.
Chibani-Chennoufi S, Bruttin A, Dillmann ML and Brussow H (2004). Phage–host interaction: an ecological perspective. Journal of Bacteriology 186: 36773686.
Connerton IF, Connerton PL, Barrow P, Seal BS and Atterbury RJ (2008). Bacteriophage therapy and Campylobacter. In: Nachamkin I, Szymanski CM and Blaser MJ (eds) Campylobacter. Washington, DC: ASM Press, pp. 679693.
Connerton PL, Loc Carrillo CM, Swift C, Dillon E, Scott A, Rees CE, Dodd CE, Frost J and Connerton IF (2004). Longitudinal study of Campylobacter jejuni bacteriophages and their hosts from broiler chickens. Applied and Environmental Microbiology 70: 38773883.
d'Herelle F (1917). Sur un microbe invisible antagoniste des bacilles dysentériques. Comptes rendus Académie Sciences 165: 373375.
Fiorentin L, Vieira ND and Barioni W Jr (2005). Oral treatment with bacteriophages reduces the concentration of Salmonella enteritidis PT4 in caecal contents of broilers. Avian Pathology 34: 258263.
Fischetti VA (2005). Bacteriophage lytic enzymes: novel anti-infectives. Trends in Microbiology 13: 491496.
Gannon VP, Graham TA, King R, Michel P, Read S, Ziebell K and Johnson RP (2002). Escherichia coli O157:H7 infection in cows and calves in a beef cattle herd in Alberta, Canada. Epidemiology and Infection 129: 163172.
Gill JJ, Pacan JC, Carson ME, Leslie KE, Griffiths MW and Sabour PM (2006a). Efficacy and pharmacokinetics of bacteriophage therapy in treatment of subclinical Staphylococcus aureus mastitis in lactating dairy cattle. Antimicrobial Agents and Chemotherapeutics 50: 29122918.
Gill JJ, Sabour PM, Leslie KE and Griffiths MW (2006b). Bovine whey proteins inhibit the interaction of Staphylococcus aureus and bacteriophage K. Journal of Applied Microbiology 101: 377386.
Greer GG (2005). Bacteriophage control of foodborne bacteria. Journal of Food Protection 68: 11021111.
Guttman B, Raya R and Kutter E (2005). Basic phage biology. In: Kutter E and Sulakvelidze A (eds) Bacteriophages Biology and Applications. Boca Raton, FL: CRC Press, pp. 2966.
Hagens S and Loessner MJ (2007). Application of bacteriophages for detection and control of foodborne pathogens. Applied Microbiology and Biotechnology 76: 513519.
Hansen VM, Rosenquist H, Baggesen DL, Brown S and Christensen BB (2007). Characterization of Campylobacter phages including analysis of host range by selected Campylobacter Penner serotypes. BMC Microbiology 7: 90.
Harris DL and Lee N (2003). Compositions and methods for reducing the amount of Salmonella in livestock. US Patent No. 6,656,463.
Higgins JP, Higgins SE, Guenther KL, Huff W, Donoghue AM, Donoghue DJ and Hargis BM (2005). Use of a specific bacteriophage treatment to reduce Salmonella in poultry products. Poultry Science 84: 11411145.
Hudson JA, Billington C, Carey-Smith G and Greening G (2005). Bacteriophages as biocontrol agents in food. Journal of Food Protection 68: 426437.
Huff WE, Huff GR, Rath NC, Balog JM, Xie H, Moore PA Jr and Donoghue AM (2002a). Prevention of Escherichia coli respiratory infection in broiler chickens with bacteriophage (SPR02). Poultry Science 81: 437441.
Huff WE, Huff GR, Rath NC, Balog JM and Donoghue AM (2002b). Prevention of Escherichia coli infection in broiler chickens with a bacteriophage aerosol spray. Poultry Science 81: 14861491.
Huff WE, Huff GR, Rath NC, Balog JM and Donoghue AM (2003a). Evaluation of aerosol spray and intramuscular injection of bacteriophage to treat an Escherichia coli respiratory infection. Poultry Science 82: 11081112.
Huff WE, Huff GR, Rath NC, Balog JM and Donoghue AM (2003b). Bacteriophage treatment of a severe Escherichia coli respiratory infection in broiler chickens. Avian Diseases 47: 13991405.
Huff WE, Huff GR, Rath NC, Balog JM and Donoghue AM (2004). Therapeutic efficacy of bacteriophage and Baytril (enrofloxacin) individually and in combination to treat colibacillosis in broilers. Poultry Science 83: 19441947.
Jamalludeen N, Johnson RP, Friendship R, Kropinski AM, Lingohr EJ and Gyles CL (2007). Isolation and characterization of nine bacteriophages that lyse O149 enterotoxigenic Escherichia coli. Veterinary Microbiology 124: 4757.
Jamalludeen N, Kropinski AM, Johnson RP, Lingohr E, Harel J and Gyles CL (2008). Complete genomic sequence of bacteriophage phiEcoM-GJ1, a novel phage that has myovirus morphology and a podovirus-like RNA polymerase. Applied and Environmental Microbiology 74: 516525.
Jorgensen F, Bailey R, Williams S, Henderson P, Wareing DR, Bolton FJ, Frost JA, Ward L and Humphrey TJ (2002). Prevalence and numbers of Salmonella and Campylobacter spp. on raw, whole chickens in relation to sampling methods. International Journal of Food Microbiology 76: 151164.
Kallings LO (1967). Sensitivity of various Salmonella strains to felix 0–1 phage. Acta Pathologica et Microbiologica Scandinavica 70: 446454.
Kropinski AM (2006). Phage therapy – everything old is new again. Canadian Journal of Infectious Diseases and Medical Microbiology 17: 297306.
Kudva IT, Jelacic S, Tarr PI, Yourderian P and Hovde CJ (1999). Biocontrol of Escherichia coli O157 with O157-specific bacteriophages. Applied and Environmental Microbiology 65: 37673773.
Laegreid WW, Elder RO and Keen JE (1999). Prevalence of Escherichia coli O157:H7 in range beef calves at weaning. Epidemiology and Infection 123: 291298.
Lee JH (2003). Methicillin (oxacillin)-resistant Staphylococcus aureus strains isolated from major food animals and their potential transmission to humans. Applied and Environmental Microbiology 69: 64896494.
Lee N and Harris DL (2001). The Effect of Bacteriophage Treatment as a Preharvest Intervention Strategy to Reduce the Rapid Dissemination of Salmonella typhimurium in Pigs. American Association of Swine Veterinarians (AASV), Perry, IA: AASV, p. 555.
Loc Carillo C, Atterbury RJ, el Shibiny A, Connerton PL, Dillon E, Scott A and Connerton IF (2005). Bacteriophage therapy to reduce Campylobacter jejuni colonization of broiler chickens. Applied and Environmental Microbiology 71: 65546563.
Luby CD and Middleton JR (2005). Efficacy of vaccination and antibiotic therapy against Staphylococcus aureus mastitis in dairy cattle. Veterinary Record 157: 8990.
Ma Y, Pacan JC, Wang Q, Xu Y, Huang X, Korenevsky A and Sabour PM (2008). Microencapsulation of bacteriophage felix O1 into chitosan-alginate microspheres for oral delivery. Applied and Environmental Microbiology 74: 47994805.
Makovec JA and Ruegg PL (2003). Antimicrobial resistance of bacteria isolated from dairy cow milk samples submitted for bacterial culture: 8,905 samples (1994–2001). Journal of the American Veterinary Medical Association 222: 15821589.
Matsuda T, Freeman TA, Hilbert DW, Duff M, Fuortes M, Stapleton PP and Daly JM (2005). Lysis-deficient bacteriophage therapy decreases endotoxin and inflammatory mediator release and improves survival in a murine peritonitis model. Surgery 137: 639646.
Matsuzaki S, Yasuda M, Nishikawa H, Kuroda M, Ujihara T, Shuin T, Shen Y, Jin Z, Fujimoto S, Nasimuzzaman MD, Wakiguchi H, Sugihara S, Sugiura T, Koda S, Muraoka A and Imai S (2003). Experimental protection of mice against lethal Staphylococcus aureus infection by novel bacteriophage phi MR11. Journal of Infectious Diseases 187: 613624.
Matthews L, McKendrick IJ, Ternent H, Gunn GJ, Synge B and Woolhouse ME (2006). Super-shedding cattle and the transmission dynamics of Escherichia coli O157. Epidemiology and Infection 134: 131142.
Maynard C, Fairbrother JM, Bekal S, Sanschagrin F, Levesque RC, Brousseau R, Masson L, Lariviere S and Harel J (2003). Antimicrobial resistance genes in enterotoxigenic Escherichia coli O149:K91 isolates obtained over a 23-year period from pigs. Antimicrobial Agents and Chemotherapeutics 47: 32143221.
Mizoguchi K, Morita M, Fischer CR, Yoichi M, Tanji Y and Unno H (2003). Coevolution of bacteriophage PP01 and Escherichia coli O157:H7 in continuous culture. Applied and Environmental Microbiology 69: 170176.
Naylor SW, Low JC, Besser TE, Mahajan A, Gunn GJ, Pearce MC, McKendrick IJ, Smith DG and Gally DL (2003). Lymphoid follicle-dense mucosa at the terminal rectum is the principal site of colonization of enterohemorrhagic Escherichia coli O157:H7 in the bovine host. Infection and Immunity 71: 15051512.
Niu YD, Xu Y, McAllister TA, Rozema EA, Stephens TP, Bach SJ, Johnson RP and Stanford K (2008). Comparison of fecal versus rectoanal mucosal swab sampling for detecting Escherichia coli O157:H7 in experimentally inoculated cattle used in assessing bacteriophage as a mitigation strategy. Journal of Food Protection 71: 691698.
Oot RA, Raya RR, Callaway TR, Edrington TS, Kutter EM and Brabban AD (2007). Prevalence of Escherichia coli O157 and O157:H7-infecting bacteriophages in feedlot cattle feces. Letters in Applied Microbiology 45: 445453.
Parisien A, Allain B, Zhang J, Mandeville R and Lan CQ (2008). Novel alternatives to antibiotics: bacteriophages, bacterial cell wall hydrolases, and antimicrobial peptides. Journal of Applied Microbiology 104: 113.
Payne RJ and Jansen VA (2003). Pharmacokinetic principles of bacteriophage therapy. Clinical Pharmacokinetics 42: 315325.
Piercy DW and West B (1976). Experimental Escherichia coli infection in broiler chickens: course of the disease induced by inoculation via the air sac route. Journal of Comparative Pathology 86: 203210.
Rangel JM, Sparling PH, Crowe C, Griffin PM and Swerdlow DL (2005). Epidemiology of Escherichia coli O157:H7 outbreaks, United States, 1982–2002. Emerging Infectious Diseases 11: 603609.
Raya RR, Varey P, Oot RA, Dyen MR, Callaway TR, Edrington TS, Kutter EM and Brabban AD (2006). Isolation and characterization of a new T-even bacteriophage, CEV1, and determination of its potential to reduce Escherichia coli O157:H7 levels in sheep. Applied and Environmental Microbiology 72: 64056410.
Rosenquist H, Nielsen NL, Sommer HM, Norrung B and Christensen BB (2003). Quantitative risk assessment of human Campylobacteriosis associated with thermophilic Campylobacter species in chickens. International Journal of Food Microbiology 83: 87103.
Sheng H, Knecht HJ, Kudva IT and Hovde CJ (2006). Application of bacteriophages to control intestinal Escherichia coli O157:H7 levels in ruminants. Applied and Environmental Microbiology 72: 53595366.
Sklar IB and Joerger RD (2001). Attempts to utilize bacteriophage to combat Salmonella enterica serovar Enteritidis infection in chickens. Journal of Food Safety 21: 1529.
Smith HW and Huggins MB (1982). Successful treatment of experimental Escherichia coli infections in mice using phage: its general superiority over antibiotics. Journal of General Microbiology 128: 218.
Smith HW and Huggins MB (1983). Effectiveness of phages in treating experimental Escherichia coli diarrhoea in calves, piglets and lambs. Journal of General Microbiology 129: 26592675.
Smith HW, Huggins MB and Shaw KM (1987a). The control of experimental Escherichia coli diarrhoea in calves by means of bacteriophages. Journal of General Microbiology 133: 11111126.
Smith HW, Huggins MB and Shaw KM (1987b). Factors influencing the survival and multiplication of bacteriophages in calves and in their environment. Journal of General Microbiology 133: 11271135.
Sulakvelidze A and Barrow P (2005). Phage therapy in animals and agribusiness. In: Kutter E and Sulakvelidze A (eds) Bacteriophages Biology and Application. Boca Raton, FL: CRC Press, pp. 335380.
Sulakvelidze A, Alavidze Z and Morris JG Jr (2001). Bacteriophage therapy. Antimicrobial Agents and Chemotherapy 45: 649659.
Summers W (2005). Bacteriophage research: early history. In: Kutter E and Sulakvelidze A (eds) Bacteriophages Biology and Applications. Boca Raton, FL: CRC Press, pp. 527.
Taylor WI and Silliker JH (1958). Hatching of eggs. U.S. Patent No. 2,851,006.
Toro H, Price SB, McKee AS, Hoerr FJ, Krehling J, Perdue M and Bauermeister L (2005). Use of bacteriophages in combination with competitive exclusion to reduce Salmonella from infected chickens. Avian Diseases 49: 118124.
Twort FW (1915). An investigation on the nature of the ultramicroscopic viruses. Lancet 189: 12411243.
Van den Bogaard AE and Stobberingh EE (2000). Epidemiology of resistance to antibiotics links between animals and humans. International Journal of Antimicrobial Agents 14: 327335.
Viscardi M, Perugini AG, Auriemma C, Capuano F, Morabito S, Kim KP, Loessner MJ and Iovane G (2008). Isolation and characterisation of two novel coliphages with high potential to control antibiotic-resistant pathogenic Escherichia coli (EHEC and EPEC). International Journal of Antimicrobial Agents 31: 152157.
Waddell T, Mazzocco A, Johnson RP, Pacan J, Campbell S, Perets A, MacKinnon J, Holtslander B and Poppe C (2000). Control of Escherichia coli O157:H7 infection of calves by bacteriophages. In: Proceedings of the 4th International Symposium and Workshop on Shiga toxin (verocytotoxin)-producing Escherichia coli (VTEC 2000) Kyoto, Japan. 29 October–2 November 2000 [abstract].
Waddell TE, Johnson RP and Mazzocco A (2004). Methods and compositions for controlled release of bioactive compounds. U.S. Patent Application No. 60/463,319.
Wagenaar JA, Van Bergen MA, Mueller MA, Wassenaar TM, Carlton RM (2005). Phage therapy reduces Campylobacter jejuni colonization in broilers. Veterinary Microbiology 109: 275283.
Weber-Dabrowska B, Mulczyk M and Gorski A (2000). Bacteriophage therapy of bacterial infections: an update of our institute's experience. Archivum Immunologiae et Therapiae Experimentalis 48: 547551.
Yoichi M, Morita M, Mizoguchi K, Fischer CR and Tanji Y (2004). The criterion for selecting effective phage for Escherichia coli control. Biochemical Engineering Journal 19: 221227.
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