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Phage Therapy Approaches to Reducing Pathogen Persistence and Transmission in Animal Production Environments: Opportunities and Challenges

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  • Authors: Anna Colavecchio1, Lawrence D. Goodridge2
  • Editors: Kalmia E. Kniel3, Siddhartha Thakur4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Food Science and Agricultural Chemistry, Food Safety and Quality Program, McGill University, Ste Anne de Bellevue, Quebec, H9X 3V9, Canada; 2: Department of Food Science and Agricultural Chemistry, Food Safety and Quality Program, McGill University, Ste Anne de Bellevue, Quebec, H9X 3V9, Canada; 3: Department of Animal and Food Science, University of Delaware, Newark, DE; 4: North Carolina State University, College of Veterinary Medicine, Raleigh, NC
  • Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.PFS-0017-2017
  • Received 09 February 2017 Accepted 28 March 2017 Published 30 June 2017
  • Lawrence D. Goodridge, lawrence.goodridge@mcgill.ca
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  • Abstract:

    The era of genomics has allowed for characterization of phages for use as antimicrobials to treat animal infections with a level of precision never before realized. As more research in phage therapy has been conducted, several advantages of phage therapy have been realized, including the ubiquitous nature, specificity, prevalence in the biosphere, and low inherent toxicity of phages, which makes them a safe and sustainable technology for control of animal diseases. These unique qualities of phages have led to several opportunities with respect to emerging trends in infectious disease treatment. However, the opportunities are tempered by several challenges to the successful implementation of phage therapy, such as the fact that an individual phage can only infect one or a few bacterial strains, meaning that large numbers of different phages will likely be needed to treat infections caused by multiple species of bacteria. In addition, phages are only effective if enough of them can reach the site of bacterial colonization, but clearance by the immune system upon introduction to the animal is a reality that must be overcome. Finally, bacterial resistance to the phages may develop, resulting in treatment failure. Even a successful phage infection and lysis of its host has consequences, because large amounts of endotoxin are released upon lysis of Gram-negative bacteria, which can lead to local and systemic complications. Overcoming these challenges will require careful design and development of phage cocktails, including comprehensive characterization of phage host range and assessment of immunological risks associated with phage treatment.

  • Citation: Colavecchio A, Goodridge L. 2017. Phage Therapy Approaches to Reducing Pathogen Persistence and Transmission in Animal Production Environments: Opportunities and Challenges. Microbiol Spectrum 5(3):PFS-0017-2017. doi:10.1128/microbiolspec.PFS-0017-2017.

Key Concept Ranking

Outer Membrane Proteins
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16s rRNA Sequencing
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References

1. World Health Organization. 2015. WHO estimates of the global burden of foodborne diseases. Foodborne diseases burden epidemiology reference group 2007–2015. http://www.who.int/foodsafety/publications/foodborne_disease/fergreport/en/.
2. Centers for Disease Control and Prevention. 2013. National Antimicrobial Resistance Monitoring System: Enteric Bacteria 2013. Human Isolates Final Report. https://www.cdc.gov/narms/pdf/2013-annual-report-narms-508c.pdf.
3. Scallan E, Hoekstra RM, Angulo FJ, Tauxe RV, Widdowson M-A, Roy SL, Jones JL, Griffin PM. 2011. Foodborne illness acquired in the United States—major pathogens. Emerg Infect Dis 17:7–15. [PubMed]
4. Lederberg J, Harrison PF. 1998. Antimicrobial Resistance: Issues and Options. National Academies Press, Washington, DC.
5. Food and Agriculture Organization of the UN. 2016. FAO calls for international action on antimicrobial resistance. http://www.fao.org/news/story/en/item/382636/icode/.
6. Levy S. 2014. Reduced antibiotic use in livestock: how Denmark tackled resistance. Environ Health Perspect 122:A160–A165. [PubMed]
7. d’Herelle F. 1917. Sur un microbe invisible antagoniste des bacilles dysentériques. CR Acad Sci Paris 165:373–375.
8. Aminov RI. 2010. A brief history of the antibiotic era: lessons learned and challenges for the future. Front Microbiol 1:134. doi:10.3389/fmicb.2010.00134.
9. Hughes P, Heritage J. 2004. Antibiotic growth-promoters in food animals. FAO Anim Prod Health Pap 129–152. http://www.fao.org/docrep/007/y5159e/y5159e08.htm.
10. Cadieux B, Colavecchio A, Goodridge L. 2016. Control of bacterial foodborne pathogens on fresh produce: a Trojan horse tale, abst. T7-O7. Annu. Meet. Int. Assoc. Food Protection, St. Louis, MO.
11. Zhang X, McDaniel AD, Wolf LE, Keusch GT, Waldor MK, Acheson DW. 2000. Quinolone antibiotics induce Shiga toxin-encoding bacteriophages, toxin production, and death in mice. J Infect Dis 181:664–670. [PubMed]
12. Pricer WE Jr, Weissbach A. 1964. The effect of lysogenic induction with Mitomycin C on the deoxyribonucleic acid polymerase of Escherichia coli K12λ. J Biol Chem 239:2607–2612. [PubMed]
13. Loś JM, Loś M, Węgrzyn A, Węgrzyn G. 2010. Hydrogen peroxide-mediated induction of the Shiga toxin-converting lambdoid prophage ST2-8624 in Escherichia coli O157:H7. FEMS Immunol Med Microbiol 58:322–329. [PubMed]
14. Colomer-Lluch M, Jofre J, Muniesa M. 2014. Quinolone resistance genes (qnrA and qnrS) in bacteriophage particles from wastewater samples and the effect of inducing agents on packaged antibiotic resistance genes. J Antimicrob Chemother 69:1265–1274. [PubMed]
15. Nilsson AS. 2014. Phage therapy: constraints and possibilities. Ups J Med Sci 119:192–198. [PubMed]
16. Canchaya C, Proux C, Fournous G, Bruttin A, Brüssow H. 2003. Prophage genomics. Microbiol Mol Biol Rev 67:238–276. [PubMed]
17. Kang HS. 2016. Comprehensive analysis of curated prophage genomes from PhiSpy for assessment of phage genome mosaicism and tRNA dependencies. M.S. thesis. San Diego State University, San Diego, CA.
18. Arthur TM, Brichta-Harhay DM, Bosilevac JM, Guerini MN, Kalchayanand N, Wells JE, Shackelford SD, Wheeler TL, Koohmaraie M. 2008. Prevalence and characterization of Salmonella in bovine lymph nodes potentially destined for use in ground beef. J Food Prot 71:1685–1688. [PubMed]
19. Enault F, Briet A, Bouteille L, Roux S, Sullivan MB, Petit M-A. 2017. Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses. ISME J 11:237–247. [PubMed]
20. Allen HK, Looft T, Bayles DO, Humphrey S, Levine UY, Alt D, Stanton TB. 2011. Antibiotics in feed induce prophages in swine fecal microbiomes. MBio 2:e00260-11. doi:10.1128/mBio.00260-11. [PubMed]
21. Labrie SJ, Samson JE, Moineau S. 2010. Bacteriophage resistance mechanisms. Nat Rev Microbiol 8:317–327. [PubMed]
22. Irbe RM, Morin LM, Oishi M. 1981. Prophage (phi 80) induction in Escherichia coli K-12 by specific deoxyoligonucleotides. Proc Natl Acad Sci USA 78:138–142. [PubMed]
23. Norris JS, Westwater C, Schofield D. 2000. Prokaryotic gene therapy to combat multidrug resistant bacterial infection. Gene Ther 7:723–725. [PubMed]
24. Westwater C, Kasman LM, Schofield DA, Werner PA, Dolan JW, Schmidt MG, Norris JS. 2003. Use of genetically engineered phage to deliver antimicrobial agents to bacteria: an alternative therapy for treatment of bacterial infections. Antimicrob Agents Chemother 47:1301–1307. [PubMed]
25. Wu K, Wood TK. 1994. Evaluation of the hok/sok killer locus for enhanced plasmid stability. Biotechnol Bioeng 44:912–921. [PubMed]
26. Jensen RB, Gerdes K. 1995. Programmed cell death in bacteria: proteic plasmid stabilization systems. Mol Microbiol 17:205–210.
27. Gerdes K, Gultyaev AP, Franch T, Pedersen K, Mikkelsen ND. 1997. Antisense RNA-regulated programmed cell death. Annu Rev Genet 31:1–31. [PubMed]
28. Couturier M, Bahassi el-M, Van Melderen L. 1998. Bacterial death by DNA gyrase poisoning. Trends Microbiol 6:269–275. [PubMed]
29. Engelberg-Kulka H, Glaser G. 1999. Addiction modules and programmed cell death and antideath in bacterial cultures. Annu Rev Microbiol 53:43–70. [PubMed]
30. Lu TK, Collins JJ. 2007. Dispersing biofilms with engineered enzymatic bacteriophage. Proc Natl Acad Sci USA 104:11197–11202. [PubMed]
31. Bikard D, Euler CW, Jiang W, Nussenzweig PM, Goldberg GW, Duportet X, Fischetti VA, Marraffini LA. 2014. Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials. Nat Biotechnol 32:1146–1150. [PubMed]
32. Citorik RJ, Mimee M, Lu TK. 2014. Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. Nat Biotechnol 32:1141–1145. [PubMed]
33. Yosef I, Manor M, Kiro R, Qimron U. 2015. Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria. Proc Natl Acad Sci USA 112:7267–7272. [PubMed]
34. Pajtasz-Piasecka E, Rossowska J, Duś D, Weber-Dąbrowska B, Zabłocka A, Górski A. 2008. Bacteriophages support anti-tumor response initiated by DC-based vaccine against murine transplantable colon carcinoma. Immunol Lett 116:24–32. [PubMed]
35. Górski A, Kniotek M, Perkowska-Ptasińska A, Mróz A, Przerwa A, Gorczyca W, Dąbrowska K, Weber-Dąbrowska B, Nowaczyk M. Bacteriophages and transplantation tolerance. Transport Proc 38:331–333.
36. Miernikiewicz P, Kłopot A, Soluch R, Szkuta P, Kęska W, Hodyra-Stefaniak K, Konopka A, Nowak M, Lecion D, Kaźmierczak Z, Majewska J, Harhala M, Górski A, Dąbrowska K. 2016. T4 phage tail adhesin Gp12 counteracts LPS-induced inflammation in vivo. Front Microbiol 7:1112. doi:10.3389/fmicb.2016.01112.
37. Nishikawa M, Hashida M, Takakura Y. 2009. Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis. Adv Drug Deliv Rev 61:319–326. [PubMed]
38. Kim K, Ingale S, Kim J, Lee S, Lee J, Kwon I, Chae B. 2014. Bacteriophage and probiotics both enhance the performance of growing pigs but bacteriophage are more effective. Anim Feed Sci Technol 196:88–95.
39. Weber-Dabrowska B, Mulczyk M, Górski A. 2003. Bacteriophages as an efficient therapy for antibiotic-resistant septicemia in man. Transplant Proc 35:1385–1386.
40. Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S. 1999. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 162:3749–3752. [PubMed]
41. Yu F, Mizushima S. 1982. Roles of lipopolysaccharide and outer membrane protein OmpC of Escherichia coli K-12 in the receptor function for bacteriophage T4. J Bacteriol 151:718–722. [PubMed]
42. Górski A, Weber-Dabrowska B. 2005. The potential role of endogenous bacteriophages in controlling invading pathogens. Cell Mol Life Sci 62:511–519. [PubMed]
43. Górski A, Ważna E, Dąbrowska B-W, Dąbrowska K, Switała-Jeleń K, Międzybrodzki R. 2006. Bacteriophage translocation. FEMS Immunol Med Microbiol 46:313–319. [PubMed]
44. Kaur T, Nafissi N, Wasfi O, Sheldon K, Wettig S, Slavcev R. 2012. Immunocompatibility of bacteriophages as nanomedicines. J Nanotechnol 2012:247427. doi:10.1155/2012/247427.
45. Hendrix RW. 2002. Bacteriophages: evolution of the majority. Theor Popul Biol 61:471–480. [PubMed]
46. Woolston J, Sulakvelidze A. 2015. Bacteriophages and food safety. eLS. doi:10.1002/9780470015902.a0025962.
47. EFSA. 2009. The use and mode of action of bacteriophages in food production. EFSA J 1076:1–26.
48. Sulakvelidze A. 2011. The challenges of bacteriophage therapy. Eur Ind Pharm 10:14–18.
49. U.S. FDA. 2015. How U.S. FDA’s GRAS notification program works. https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/ucm083022.htm.
50. U.S. FDA. 2015. From an idea to the marketplace: the journey of an animal drug through the approval process. https://www.fda.gov/AnimalVeterinary/ResourcesforYou/AnimalHealthLiteracy/ucm219207.htm.
51. Chan BK, Abedon ST, Loc-Carrillo C. 2013. Phage cocktails and the future of phage therapy. Future Microbiol 8:769–783. [PubMed]
52. Majewska J, Beta W, Lecion D, Hodyra-Stefaniak K, Kłopot A, Kaźmierczak Z, Miernikiewicz P, Piotrowicz A, Ciekot J, Owczarek B, Kopciuch A, Wojtyna K, Harhala M, Mąkosa M, Dąbrowska K. 2015. Oral application of T4 phage induces weak antibody production in the gut and in the blood. Viruses 7:4783–4799. [PubMed]
53. Sulakvelidze A, Kutter E. 2004. Bacteriophage therapy in humans, p. 381. In Kutter E, Sulakvelidze S (ed), Bacteriophages: Biology and Applications. CRC Press, Boca Raton, FL.
54. Merril CR, Biswas B, Carlton R, Jensen NC, Creed GJ, Zullo S, Adhya S. 1996. Long-circulating bacteriophage as antibacterial agents. Proc Natl Acad Sci USA 93:3188–3192. [PubMed]
55. Capparelli R, Ventimiglia I, Roperto S, Fenizia D, Iannelli D. 2006. Selection of an Escherichia coli O157:H7 bacteriophage for persistence in the circulatory system of mice infected experimentally. Clin Microbiol Infect 12:248–253. [PubMed]
56. Kim KP, Cha JD, Jang EH, Klumpp J, Hagens S, Hardt WD, Lee KY, Loessner MJ. 2008. PEGylation of bacteriophages increases blood circulation time and reduces T-helper type 1 immune response. Microb Biotechnol 1:247–257. [PubMed]
57. Smith HW, Huggins MB, Shaw KM. 1987. Factors influencing the survival and multiplication of bacteriophages in calves and in their environment. J Gen Microbiol 133:1127–1135. [PubMed]
58. Colom J, Cano-Sarabia M, Otero J, Cortés P, Maspoch D, Llagostera M. 2015. Liposome-encapsulated bacteriophages for enhanced oral phage therapy against Salmonella spp. Appl Environ Microbiol 81:4841–4849. [PubMed]
59. Ma Y, Pacan JC, Wang Q, Xu Y, Huang X, Korenevsky A, Sabour PM. 2008. Microencapsulation of bacteriophage felix O1 into chitosan-alginate microspheres for oral delivery. Appl Environ Microbiol 74:4799–4805. [PubMed]
60. Luria SE, Delbrück M. 1943. Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28:491–511. [PubMed]
61. Lindberg AA. 1973. Bacteriophage receptors. Annu Rev Microbiol 27:205–241. [PubMed]
62. Goodridge LD. 2010. Design of phage cocktails for therapy from a host range point of view. In Villa TG, Veiga-Crespo P (ed), Enzybiotics: Antibiotic Enzymes as Drugs and Therapeutics. John Wiley, Hoboken, NJ.
63. Tanji Y, Shimada T, Yoichi M, Miyanaga K, Hori K, Unno H. 2004. Toward rational control of Escherichia coli O157:H7 by a phage cocktail. Appl Microbiol Biotechnol 64:270–274. [PubMed]
64. Chase J, Kalchayanand N, Goodridge LD. 2005. Use of bacteriophage therapy to reduce Escherichia coli O157:H7 concentrations in an anaerobic digestor that stimulates the bovine gastrointestinal tract. Institute of Food Technologists Annual Meeting and Food Expo, New Orleans, Louisiana.
65. Hagens S, Bläsi U. 2003. Genetically modified filamentous phage as bactericidal agents: a pilot study. Lett Appl Microbiol 37:318–323. [PubMed]
66. Hagens S, Habel A, von Ahsen U, von Gabain A, Bläsi U. 2004. Therapy of experimental Pseudomonas infections with a nonreplicating genetically modified phage. Antimicrob Agents Chemother 48:3817–3822. [PubMed]
67. World Health Organization. 2014. WHO’s first global report on antibiotic resistance reveals serious, worldwide threat to public health. http://www.who.int/mediacentre/news/releases/2014/amr-report/en/.
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2017-06-30
2017-09-23

Abstract:

The era of genomics has allowed for characterization of phages for use as antimicrobials to treat animal infections with a level of precision never before realized. As more research in phage therapy has been conducted, several advantages of phage therapy have been realized, including the ubiquitous nature, specificity, prevalence in the biosphere, and low inherent toxicity of phages, which makes them a safe and sustainable technology for control of animal diseases. These unique qualities of phages have led to several opportunities with respect to emerging trends in infectious disease treatment. However, the opportunities are tempered by several challenges to the successful implementation of phage therapy, such as the fact that an individual phage can only infect one or a few bacterial strains, meaning that large numbers of different phages will likely be needed to treat infections caused by multiple species of bacteria. In addition, phages are only effective if enough of them can reach the site of bacterial colonization, but clearance by the immune system upon introduction to the animal is a reality that must be overcome. Finally, bacterial resistance to the phages may develop, resulting in treatment failure. Even a successful phage infection and lysis of its host has consequences, because large amounts of endotoxin are released upon lysis of Gram-negative bacteria, which can lead to local and systemic complications. Overcoming these challenges will require careful design and development of phage cocktails, including comprehensive characterization of phage host range and assessment of immunological risks associated with phage treatment.

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FIGURE 1

Intrinsic and extrinsic characteristics that may contribute to the success or failure of bacteriophage therapy.

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.PFS-0017-2017
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TABLE 1

Currently approved and commercially available bacteriophage-based products to reduce the presence of foodborne pathogen and spoilage bacteria in foods and food animals

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.PFS-0017-2017

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