Recently, a number of phage therapy phase I and II safety trials have been concluded, showing no notable safety concerns associated with the use of phage. Though hurdles for efficient treatment remain, these trials hold promise for future phase III clinical trials. Interestingly, most phage formulations used in these clinical trials are straightforward phage suspensions, and not much research has focused on the processing of phage cocktails in specific pharmaceutical dosage forms. Additional research on formulation strategies and the stability of phage-based drugs will be of key importance, especially with phage therapy advancing toward phase III clinical trials.


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Literature Cited

  1. Endersen L, O'Mahony J, Hill C, Ross RP, McAuliffe O, Coffey A. 1.  2014. Phage therapy in the food industry. Annu. Rev. Food Sci. Technol. 5:327–49 [Google Scholar]
  2. Brovko LY, Anany H, Griffiths MW. 2.  2012. Bacteriophages for detection and control of bacterial pathogens in food and food-processing environment. Adv. Food Nutr. Res. 67:241–88 [Google Scholar]
  3. Sillankorva SM, Oliveira H, Azeredo J. 3.  2012. Bacteriophages and their role in food safety. Int. J. Microbiol. 2012:1–13 [Google Scholar]
  4. Tomlinson IM. 4.  2004. Next-generation protein drugs. Nat. Biotechnol. 22:521–22 [Google Scholar]
  5. Sandeep K. 5.  2006. Bacteriophage precision drug against bacterial infections. Curr. Sci. 90:631–33 [Google Scholar]
  6. Bruttin A, Brüssow H. 6.  2005. Human volunteers receiving Escherichia coli phage T4 orally: a safety test of phage therapy. Antimicrob. Agents Chemother. 49:2874–78 [Google Scholar]
  7. Gill JJ, Hyman P. 7.  2010. Phage choice, isolation, and preparation for phage therapy. Curr. Pharm. Biotechnol. 11:2–14 [Google Scholar]
  8. Ackermann HW, Tremblay D, Moineau S. 8.  2004. Long-term bacteriophage preservation. WFCC Newsl. 38:35–40 [Google Scholar]
  9. Tovkach FI, Zhuminska GI, Kushkina AI. 9.  2012. Long-term preservation of unstable bacteriophages of enterobacteria. Mikrobiol. Zhurnal 74:60–66 [Google Scholar]
  10. Jończyk E, Kłak M, Międzybrodzki R, Górski A. 10.  2011. The influence of external factors on bacteriophages. Folia Microbiol. 56:191–200 [Google Scholar]
  11. Vagenende V, Yap MGS, Trout BL. 11.  2009. Mechanisms of protein stabilization and prevention of protein aggregation by glycerol. Biochemistry 48:11084–96 [Google Scholar]
  12. Wang W. 12.  2000. Lyophilization and development of solid protein pharmaceuticals. Int. J. Pharm. 203:1–60 [Google Scholar]
  13. Ameri M, Maa YF. 13.  2006. Spray drying of biopharmaceuticals: stability and process considerations. Drying Technol. 24:763–68 [Google Scholar]
  14. Crowe LM, Reid DS, Crowe JH. 14.  1996. Is trehalose special for preserving dry biomaterials?. Biophys. J. 71:2087–93 [Google Scholar]
  15. Merabishvili M, Vervaet C, Pirnay JP, De Vos D, Verbeken G. 15.  et al. 2013. Stability of Staphylococcus aureus phage ISP after freeze-drying (lyophilization). PLOS ONE 8:e68797 [Google Scholar]
  16. Vandenheuvel D, Singh A, Vandersteegen K, Klumpp J, Lavigne R, Van den Mooter G. 16.  2013. Feasibility of spray drying bacteriophages into respirable powders to combat pulmonary bacterial infections. Eur. J. Pharm. Biopharm. 84:578–82 [Google Scholar]
  17. Vandenheuvel D, Meeus J, Lavigne R, Van den Mooter G. 17.  2014. Instability of bacteriophages in spray-dried trehalose powders is caused by crystallization of the matrix. Int. J. Pharm. 472:202–5 [Google Scholar]
  18. Ma Y, Pacan JC, Wang Q, Xu Y, Huang X. 18.  et al. 2008. Microencapsulation of bacteriophage Felix O1 into chitosan-alginate microspheres for oral delivery. Appl. Environ. Microbiol. 74:4799–805 [Google Scholar]
  19. Golshahi L, Seed KD, Dennis JJ, Finlay WH. 19.  2008. Toward modern inhalational bacteriophage therapy: nebulization of bacteriophages of Burkholderia cepacia complex. J. Aerosol Med. Pulm. Drug Deliv. 21:351–60 [Google Scholar]
  20. Semler DD, Lynch KH, Dennis JJ. 20.  2012. The promise of bacteriophage therapy for Burkholderia cepacia complex respiratory infections. Front. Cell. Infect. Microbiol. 1:27 [Google Scholar]
  21. Hoe S, Semler DD, Goudie AD, Lynch KH, Matinkhoo S. 21.  et al. 2013. Respirable bacteriophages for the treatment of bacterial lung infections. J. Aerosol Med. Pulm. Drug Deliv. 26:317–35 [Google Scholar]
  22. Tsonos J, Oosterik LH, Tuntufye HN, Klumpp J, Butaye P. 22.  et al. 2014. A cocktail of in vitro efficient phages is not a guarantee for in vivo therapeutic results against avian colibacillosis. Vet. Microbiol. 171:470–79 [Google Scholar]
  23. Merabishvili M, Pirnay JP, Verbeken G, Chanishvili N, Tediashvili M. 23.  et al. 2009. Quality-controlled small-scale production of a well-defined bacteriophage cocktail for use in human clinical trials. PLOS ONE 4:e4944 [Google Scholar]
  24. Borie C, Sánchez ML, Navarro C, Ramírez S, Morales MA. 24.  et al. 2009. Aerosol spray treatment with bacteriophage and competitive exclusion reduces Salmonella enteritidis infection in chickens. Avian Dis. 53:250–54 [Google Scholar]
  25. Fortier LC, Moineau S. 25.  2009. Phage production and maintenance of stocks, including expected stock lifetimes. Bacteriophages: Methods and Protocols 1 Isolation, Characterization, and Interactions MRJ Clokie, AM Kropinski 203–19 New York: Humana [Google Scholar]
  26. Cooper CJ, Denyer SP, Maillard JY. 26.  2014. Stability and purity of a bacteriophage cocktail preparation for nebulizer delivery. Lett. Appl. Microbiol. 58:118–22 [Google Scholar]
  27. Wright A, Hawkins CH, Änggård EE, Harper DR. 27.  2009. A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa: a preliminary report of efficacy. Clin. Otolaryngol. 34:349–57 [Google Scholar]
  28. Golec P, Dąbrowski K, Hejnowicz MS, Gozdek A, Łoś JM. 28.  et al. 2011. A reliable method for storage of tailed phages. J. Microbiol. Methods 84:486–89 [Google Scholar]
  29. Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. 29.  2010. Stability of protein pharmaceuticals: an update. Pharm. Res. 27:544–75 [Google Scholar]
  30. Schade AL, Caroline L. 30.  1943. The preparation of a polyvalent dysentery bacteriophage in a dry and stable form. I. Preliminary investigations and general procedures. J. Bacteriol. 46:463–73 [Google Scholar]
  31. Zierdt CH. 31.  1988. Stabilities of lyophilized Staphylococcus aureus typing bacteriophages. Appl. Environ. Microbiol. 54:2590 [Google Scholar]
  32. Zierdt CH. 32.  1959. Preservation of staphylococcal bacteriophage by means of lyophilization. Am. J. Clin. Pathol. 31:326–31 [Google Scholar]
  33. Clark WA. 33.  1962. Comparison of several methods for preserving bacteriophages. Appl. Microbiol. 10:466–71 [Google Scholar]
  34. Schade AL, Caroline L. 34.  1944. The preparation of a polyvalent dysentery bacteriophage in a dry and stable form. II. Factors affecting the stabilization of dysentery bacteriophage during lyophilization. J. Bacteriol. 48:179–90 [Google Scholar]
  35. Schade AL, Caroline L. 35.  1944. The preparation of a polyvalent dysentery bacteriophage in a dry and stable form. III. Stability of the dried bacteriophage towards heat, humidity, age and acidity. J. Bacteriol. 48:243–51 [Google Scholar]
  36. Puapermpoonsiri U, Ford SJ, van der Walle CF. 36.  2010. Stabilization of bacteriophage during freeze drying. Int. J. Pharm. 389:168–75 [Google Scholar]
  37. Alfadhel M, Puapermpoonsiri U, Ford SJ, McInnes FJ, van der Walle CF. 37.  2011. Lyophilized inserts for nasal administration harboring bacteriophage selective for Staphylococcus aureus: in vitro evaluation. Int. J. Pharm. 416:280–87 [Google Scholar]
  38. Golshahi L, Lynch KH, Dennis JJ, Finlay WH. 38.  2011. In vitro lung delivery of bacteriophages KS4-M and ϕKZ using dry powder inhalers for treatment of Burkholderia cepacia complex and Pseudomonas aeruginosa infections in cystic fibrosis. J. Appl. Microbiol. 110:106–17 [Google Scholar]
  39. Anany H, Chen W, Pelton R, Griffiths MW. 39.  2011. Biocontrol of Listeria monocytogenes and Escherichia coli O157:H7 in meat by using phages immobilized on modified cellulose membranes. Appl. Environ. Microbiol. 77:6379–87 [Google Scholar]
  40. Markoishvili K, Tsitlanadze G, Katsarava R, Morris JGJ, Sulakvelidze A. 40.  2002. A novel sustained-release matrix based on biodegradable poly(ester amide)s and impregnated with bacteriophages and an antibiotic shows promise in management of infected venous stasis ulcers and other poorly healing wounds. Int. J. Dermatol. 41:453–58 [Google Scholar]
  41. Jikia D, Chkhaidze N, Imedashvili E, Mgaloblishvili I, Tsitlanadze G. 41.  et al. 2005. The use of a novel biodegradable preparation capable of the sustained release of bacteriophages and ciprofloxacin, in the complex treatment of multidrug-resistant Staphylococcus aureus-infected radiation injuries caused by exposure to Sr90. Clin. Exp. Dermatol. 30:23–26 [Google Scholar]
  42. Kutter E, De Vos D, Gvasalia G, Alavidze Z, Gogokhia L. 42.  et al. 2010. Phage therapy in clinical practice: treatment of human infections. Curr. Pharm. Biotechnol. 11:69–86 [Google Scholar]
  43. Sulakvelidze A, Kutter E. 43.  2004. Bacteriophage therapy in humans. Bacteriophages: Biology and Applications E Kutter, A Sulakvelidze 381–436 Boca Raton, FL: CRC Press [Google Scholar]
  44. Ohtake S, Martin RA, Yee L, Chen D, Kristensen DD. 44.  et al. 2010. Heat-stable measles vaccine produced by spray drying. Vaccine 28:1275–84 [Google Scholar]
  45. Matinkhoo S, Lynch KH, Dennis JJ, Finlay WH, Vehring R. 45.  2011. Spray-dried respirable powders containing bacteriophages for the treatment of pulmonary infections. J. Pharm. Sci. 100:5197–205 [Google Scholar]
  46. Carpenter JF, Crowe JH. 46.  1989. An infrared spectroscopic study of the interactions of carbohydrates with dried proteins. Biochemistry 28:3916–22 [Google Scholar]
  47. Franks F, Hatley RHM, Mathias SF. 47.  1991. Material science and the production of shelf stable biologicals. Pharm. Technol. Int. 3:24–34 [Google Scholar]
  48. Alvarez-Gonzalez E, Alfadhel M, Mane P, Ford SJ, Moore BD, van der Walle CF. 48.  2012. Bioprocessing of bacteriophages via rapid drying onto microcrystals. Biotechnol. Prog. 28:540–48 [Google Scholar]
  49. Puapermpoonsiri U, Spencer J, van der Walle CF. 49.  2009. A freeze-dried formulation of bacteriophage encapsulated in biodegradable microspheres. Eur. J. Pharm. Biopharm. 72:26–33 [Google Scholar]
  50. O'Flaherty S, Ross RP, Meaney W, Fitzgerald GF, Elbreki MF, Coffey A. 50.  2005. Potential of the polyvalent anti-Staphylococcus bacteriophage K for control of antibiotic-resistant staphylococci from hospitals. Appl. Environ. Microbiol. 71:1836–42 [Google Scholar]
  51. Esteban PP, Alves DR, Enright MC, Bean JE, Gaudion A. 51.  et al. 2014. Enhancement of the antimicrobial properties of bacteriophage-K via stabilization using oil-in-water nano-emulsions. Biotechnol. Prog. 30:932–44 [Google Scholar]
  52. Veronese FM, Pasut G. 52.  2005. PEGylation, successful approach to drug delivery. Drug Discov. Today 10:1451–58 [Google Scholar]
  53. Kim KP, Cha JD, Jang EH, Klumpp J, Hagens S. 53.  et al. 2008. PEGylation of bacteriophages increases blood circulation time and reduces T-helper type 1 immune response. Microb. Biotechnol. 1:247–57 [Google Scholar]
  54. Merril CR, Biswas B, Carlton RM, Jensen NC, Creed GJ. 54.  et al. 1996. Long-circulating bacteriophage as antibacterial agents. PNAS 93:3188–92 [Google Scholar]
  55. Vitiello CL, Merril CR, Adhya S. 55.  2005. An amino acid substitution in a capsid protein enhances phage survival in mouse circulatory system more than a 1000-fold. Virus Res. 114:101–3 [Google Scholar]
  56. Canchaya C, Proux C, Fournous G, Bruttin A, Brüssow H. 56.  2003. Prophage genomics. Microbiol. Mol. Biol. Rev. 67:238–76 [Google Scholar]
  57. Brüssow H, Canchaya C, Hardt WD. 57.  2004. Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol. Mol. Biol. Rev. 68:560–602 [Google Scholar]
  58. Sarker SA, McCallin S, Barretto C, Berger B, Pittet AC. 58.  et al. 2012. Oral T4-like phage cocktail application to healthy adult volunteers from Bangladesh. Virology 434:222–32 [Google Scholar]
  59. McCallin S, Alam Sarker S, Barretto C, Sultana S, Berger B. 59.  et al. 2013. Safety analysis of a Russian phage cocktail: from metagenomic analysis to oral application in healthy human subjects. Virology 443:187–96 [Google Scholar]
  60. Yang J, Chen L, Sun L, Yu J, Jin Q. 60.  2008. VFDB 2008 release: an enhanced web-based resource for comparative pathogenomics. Nucleic Acids Res. 36:D539–42 [Google Scholar]
  61. Liu B, Pop M. 61.  2009. ARDB—Antibiotic Resistance Genes Database. Nucleic Acids Res. 37:D443–47 [Google Scholar]
  62. Muniesa M, Imamovic L, Jofre J. 62.  2011. Bacteriophages and genetic mobilization in sewage and faecally polluted environments. Microb. Biotechnol. 4:725–34 [Google Scholar]
  63. Kunisaki H, Tanji Y. 63.  2010. Intercrossing of phage genomes in a phage cocktail and stable coexistence with Escherichia coli O157:H7 in anaerobic continuous culture. Appl. Microbiol. Biotechnol. 85:1533–40 [Google Scholar]
  64. Santos SB, Fernandes E, Carvalho CM, Sillankorva S, Krylov VN. 64.  et al. 2010. Selection and characterization of a multivalent Salmonella phage and its production in a nonpathogenic Escherichia coli strain. Appl. Environ. Microbiol. 76:7338–42 [Google Scholar]
  65. Broxmeyer L, Sosnowska D, Miltner E, Chacón O, Wagner D. 65.  et al. 2002. Killing of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens. J. Infect. Dis. 186:1155–60 [Google Scholar]
  66. Brüssow H. 66.  2001. Phages of dairy bacteria. Annu. Rev. Microbiol. 55:283–303 [Google Scholar]
  67. Desier F, McShan WM, van Sinderen D, Ferretti JJ, Brüssow H. 67.  2001. Comparative genomics reveals close genetic relationships between phages from dairy bacteria and pathogenic streptococci: evolutionary implications for prophage-host interactions. Virology 288:325–41 [Google Scholar]
  68. Oh J, Byrd AL, Deming C, Conlan S. 68.  NISC Comp. Seq. Program et al. 2014. Biogeography and individuality shape function in the human skin metagenome. Nature 514:59–64 [Google Scholar]
  69. Reyes A, Haynes M, Hanson N, Angly FE, Heath AC. 69.  et al. 2010. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466:334–38 [Google Scholar]
  70. Suttle CA. 70.  2005. Viruses in the sea. Nature 437:356–61 [Google Scholar]
  71. Chibani-Chennoufi S, Sidoti J, Bruttin A, Kutter E, Sarker S, Brüssow H. 71.  2004. In vitro and in vivo bacteriolytic activities of Escherichia coli phages: implications for phage therapy. Antimicrob. Agents Chemother. 48:2558–69 [Google Scholar]
  72. Weiss M, Denou E, Vruttin A, Serra-Moreno R, Dillmann ML, Brüssow H. 72.  2009. In vivo replication of T4 and T7 bacteriophages in germ-free mice colonized with Escherichia coli. Virology 393:16–23 [Google Scholar]
  73. Chibani-Chennoufi S, Sidoti J, Bruttin A, Dillmann ML, Kutter E. 73.  et al. 2004. Isolation of Escherichia coli bacteriophages from the stool of pediatric diarrhea patients in Bangladesh. J. Bacteriol. 186:8287–94 [Google Scholar]
  74. Rose T, Verbeken G, De Vos D, Merabishvili M, Vaneechoute M. 74.  et al. 2014. Experimental phage therapy of burn wound infection: difficult first steps. Int. J. Burns Trauma 4:66–73 [Google Scholar]
  75. Verbeken G, De Vos D, Vaneechoute M, Merabishvili M, Zizi M, Pirnay JP. 75.  2007. European regulatory conundrum of phage therapy. Future Microbiol. 2:485–91 [Google Scholar]
  76. Pirnay JP, De Vos D, Verbeken G, Merabishvili M, Chanishvili N. 76.  et al. 2011. The phage therapy paradigm: prêt-à-porter or sur-mesure?. Pharm. Res. 28:934–37 [Google Scholar]
  77. Pirnay JP, Blasdel BG, Bretaudeau L, Buckling A, Chanishvili N. 77.  et al. 2015. Quality and safety requirements for sustainable phage therapy products. Pharm. Res. 32:2173–79 [Google Scholar]
  78. Pirnay JP, Verbeken G, Rose T, Jennes S, Zizi M. 78.  et al. 2012. Introducing yesterday's phage therapy in today's medicine. Future Virol. 7:379–90 [Google Scholar]
  79. Międzybrodzki R, Borysowski J, Weber-Dąbrowska B, Fortuna W, Letkiewicz S. 79.  et al. 2012. Clinical aspects of phage therapy. Adv. Virus Res. 83:73–121 [Google Scholar]
  80. Parracho HMRT, Burrowes BH, Enright MC, McConville ML, Harper DR. 80.  2012. The role of regulated clinical trials in the development of bacteriophage therapeutics. J. Mol. Genet. Med. 6:279–86 [Google Scholar]
  81. Verbeken G, Pirnay JP, Lavigne R, Jennes S, De Vos D. 81.  et al. 2014. Call for a dedicated European legal framework for bacteriophage therapy. Arch. Immunol. Ther. Exp. 62:117–29 [Google Scholar]
  82. Huys I, Pirnay JP, Lavigne R, Jennes S, De Vos D. 82.  et al. 2013. Paving a regulatory pathway for phage therapy: Europe should muster the resources to financially, technically and legally support the introduction of phage therapy. EMBO Rep. 14:951–54 [Google Scholar]
  83. Verbeken G, Huys I, Pirnay JP, Jennes S, Chanishvili N. 83.  et al. 2014. Taking bacteriophage therapy seriously: a moral argument. Biomed. Res. Int. 2014:1–8 [Google Scholar]
  84. Reardon S. 84.  2014. Phage therapy gets revitalized. Nature 510:15–16 [Google Scholar]
  85. Matsuzaki S, Uchiyama J, Takemura-Uchiyama I, Daibata M. 85.  2014. Perspective: the age of the phage. Nature 509:S9 [Google Scholar]
  86. Fogelman I, Davey V, Ochs HD, Elashoff M, Feinberg MB. 86.  et al. 2000. Evaluation of CD4+ T cell function in vivo in HIV-infected patients as measured by bacteriophage phiX174 immunization. J. Infect. Dis. 182:435–41 [Google Scholar]
  87. Rubinstein A, Mizrachi Y, Bernstein L, Shliozberg J, Golodner M. 87.  et al. 2000. Progressive specific immune attrition after primary, secondary and tertiary immunizations with bacteriophage ϕX174 in asymptomatic HIV-1 infected patients. AIDS 14:F55–62 [Google Scholar]
  88. Ochs HD, Davis SD, Wedgewood RJ. 88.  1971. Immunologic responses to bacteriophage ϕX 174 in immunodeficiency diseases. J. Clin. Investig. 50:2559–68 [Google Scholar]
  89. Rhoads DD, Wolcott RD, Kuskowski MA, Wolcott BM, Ward LS, Sulakvelidze A. 89.  2009. Bacteriophage therapy of venous leg ulcers in humans: results of a phase I safety trial. J. Wound Care 18:237–43 [Google Scholar]
  90. Grice EA, Kong HH, Renaud G, Young AC, Bouffard GG. 90.  et al. 2008. A diversity profile of the human skin microbiota. Genome Res. 18:1043–50 [Google Scholar]
  91. Marza JAS, Soothill JS, Boydell P, Collyns TA. 91.  2006. Multiplication of therapeutically administered bacteriophages in Pseudomonas aeruginosa infected patients. Burns 32:644–46 [Google Scholar]
  92. Weber-Dąbrowska B, Mulczyk M, Górski A. 92.  2000. Bacteriophage therapy of bacterial infections: an update of our institute's experience. Arch. Immunol. Ther. Exp. 48:547–51 [Google Scholar]
  93. Denou E, Bruttin A, Barretto C, Ngom-Bru C, Brüssow H, Zuber S. 93.  2009. T4 phages against Escherichia coli diarrhea: potential and problems. Virology 388:21–30 [Google Scholar]
  94. Zuber S, Ngom-Bru C, Barretto C, Bruttin A, Brüssow H, Denou E. 94.  2007. Genome analysis of phage JS98 defines a fourth major subgroup of T4-like phages in Escherichia coli. J. Bacteriol. 189:8206–14 [Google Scholar]
  95. Bourdin G, Schmitt B, Mavin Guy L, Germond JE, Zuber S. 95.  et al. 2014. Amplification and purification of T4-like Escherichia coli phages for phage therapy: from laboratory to pilot scale. Appl. Environ. Microbiol. 80:1469–76 [Google Scholar]
  96. Bourdin G, Navarro A, Sarker SA, Pittet AC, Qadri F. 96.  et al. 2014. Coverage of diarrhoea-associated Escherichia coli isolates from different origins with two types of phage cocktails. Microb. Biotechnol. 7:165–76 [Google Scholar]
  97. Sarker SA, Sultana S, Fuchs GJ, Alam NH, Azim T. 97.  et al. 2005. Lactobacillus paracasei strain ST11 has no effect on rotavirus but ameliorates the outcome of nonrotavirus diarrhea in children from Bangladesh. Pediatrics 116:e221–28 [Google Scholar]
  98. Hurley JC. 98.  1992. Antibiotic-induced release of endotoxin: a reappraisal. Clin. Infect. Dis. 15:840–54 [Google Scholar]
  99. Cook GC. 99.  1985. Infective gastroenteritis and its relationship to reduced gastric acidity. Scand. J. Gastroenterol. Suppl. 111:17–23 [Google Scholar]
  100. Maura D, Morello E, du Merle L, Bomme P, Le Bouguénec C, Debarbieux L. 100.  2012. Intestinal colonization by enteroaggregative Escherichia coli supports long-term bacteriophage replication in mice. Environ. Microbiol. 14:1844–54 [Google Scholar]
  101. Debarbieux L. 101.  2014. Bacterial sensing of bacteriophages in communities: the search for the Rosetta stone. Curr. Opin. Microbiol. 20:125–30 [Google Scholar]
  102. Reyes A, Wu M, McNulty NP, Rohwer FL, Gordon JI. 102.  2013. Gnotobiotic mouse model of phage-bacterial host dynamics in the human gut. PNAS 110:20236–41 [Google Scholar]
  103. Wiggins B, Alexander M. 103.  1985. Minimum bacterial density for bacteriophage replication: implications for significance of bacteriophages in natural ecosystems. Appl. Environ. Microbiol. 49:19–23 [Google Scholar]
  104. Barletta F, Ochoa TJ, Mercado E, Ruiz J, Ecker L. 104.  et al. 2011. Quantitative real-time polymerase chain reaction for enteropathogenic Escherichia coli: a tool for investigation of asymptomatic versus symptomatic infections. Clin. Infect. Dis. 53:1223–29 [Google Scholar]
  105. Albert MJ, Farugue AS, Farugue SM, Sack RB, Mahalanabis D. 105.  1999. Case-control study of enteropathogens associated with childhood diarrhea in Dhaka, Bangladesh. J. Clin. Microbiol. 37:3458–64 [Google Scholar]
  106. Brüssow H. 106.  2013. Bacteriophage-host interaction: from splendid isolation into a messy reality. Curr. Opin. Microbiol. 16:500–6 [Google Scholar]
  107. Babalova EG, Katsitadze KT, Sakvarelidze LA, Imnaishvili NS, Sharashidze TG. 107.  et al. 1968. Preventive value of dried dysentery bacteriophage. Zhurnal Mikrobiol. Epidemiol. Immunol. 45:143–45 (In Russian) [Google Scholar]
  108. Sulakvelidze A, Alavidze Z, Morris JG. 108.  2001. Bacteriophage therapy. Antimicrob. Agents Chemother. 45:649–59 [Google Scholar]
  109. Jones JB, Vallad GE, Iriarte FB, Obradović A, Wernsing MH. 109.  et al. 2012. Considerations for using bacteriophages for plant disease control. Bacteriophage 2:208–14 [Google Scholar]
  110. Tsonos J, Vandenheuvel D, Briers Y, De Greve H, Hernalsteens JP, Lavigne R. 110.  2014. Hurdles in bacteriophage therapy: deconstructing the parameters. Vet. Microbiol. 171:460–69 [Google Scholar]
  111. Johnson RP, Gyles CL, Huff WE, Ojha S, Huff GR. 111.  et al. 2008. Bacteriophages for prophylaxis and therapy in cattle, poultry and pigs. Anim. Health Res. Rev. 9:201–15 [Google Scholar]

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