Abstract
High quantities of bacteriophages are currently used in the food industry and agriculture. However, growing antibiotic resistance of bacteria has recently awakened the interest to use bacteriophages for the treatment of bacterial infections in humans indicating that even higher quantities will be required in the future. High demand combined with a wide range of applications requires also efficient bacteriophage production processes operating at low production costs and with high productivity. To achieve this goal, different approaches were introduced and extensive studies of various parameters affecting bacteriophage formation were investigated. In this mini-review, we provide a short overview about different operation modes of bacteriophage production such as batch, semi-continuous and especially continuous with the pros and cons of each. We present factors affecting bacterial physiological state, its effect on phage formation and provide a description of methods for determination of bacteriophage growth parameters, through which bacteriophage formation is obtained. Understanding of described phenomena and inclusion of potential occurrence of mutations and selection in continuous systems enables evaluation of continuous process productivity and its optimization.
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References
Abedon ST (2018) Phage Companies. http://companies.phage.org/. Accessed 14 June 2018
Abedon ST, Herschler TD, Stopar D (2001) Bacteriophage latent-period evolution as a response to resource availability. Appl Environ Microbiol 67:4233–4241
Abedon ST, Kuhl SJ, Blasdel BG, Kutter EM (2011) Phage treatment of human infections. Bacteriophage 1:66–85. https://doi.org/10.4161/bact.1.2.15845
Adams MH (1959) Bacteriophages. Interscience publishers, Inc., New York
Agboluaje M, Sauvageau D (2018) Bacteriophage production in bioreactors. In: Azeredo J, Sillankorva S (eds) Bacteriophage therapy. Methods in molecular biology, vol 1693. Humana Press, New York, pp 173–193. doi: https://doi.org/10.1007/978-1-4939-7395-8_15
Ahmed K, Kaderbhai NN, Kaderbhai MA (2012) Bacteriophage therapy revisited. African J Microbiol Res 6:3366–3379. https://doi.org/10.5897/AJMR11.968
Aita T, Husimi Y (1994) Period dependent selection in continuous culture of viruses in a periodic environment. J Theor Biol 168:281–289. https://doi.org/10.1006/jtbi.1994.1109
AmpliPhi Biosciences Corporation (2018) http://www.ampliphibio.com/about-us/. Accessed 28 June 2018
Anderson TF (1949) The reactions of bacterial viruses with their host cells. Bot Rev 15:464–505. https://doi.org/10.1007/BF02861677
Balogh B, Jones JB, Iriarte FB, Momol MT (2010) Phage therapy for plant disease control. Curr Pharm Biotechnol 11:48–57
Barrow PA (2001) The use of bacteriophages for treatment and prevention of bacterial disease in animals and animal models of human infection. J Chem Technol Biotechnol 76:677–682. https://doi.org/10.1002/jctb.436
Bohannan BJM, Lenski RE (1997) Effect of resource enrichment on a chemostat community of bacteria and bacteriophage. Ecology 78:2303–2315
Bohannan BJM, Lenski RE (2000) The relative importance of competition and predation varies with productivity in a model community. Am Nat 156:329–340. https://doi.org/10.1086/303393
Branston S, Stanley E, Ward J, Keshavarz-Moore E (2011) Study of robustness of filamentous bacteriophages for industrial applications. Biotechnol Bioeng 108:1468–1472. https://doi.org/10.1002/bit.23066
Bryan D, El-Shibiny A, Hobbs Z, Porter J, Kutter EM (2016) Bacteriophage T4 infection of stationary phase E. coli: life after log from a phage perspective. Front Microbiol 7:1391. https://doi.org/10.3389/fmicb.2016.01391
Bull JJ (2006) Optimality models of phage life history and parallels in disease evolution. J Theor Biol 241:928–938. https://doi.org/10.1016/j.jtbi.2006.01.027
Bull JJ, Millstein J, Orcutt J, Wichman HA (2006) Evolutionary feedback mediated through population density, illustrated with viruses in chemostats. Am Nat 167:E39–E51. https://doi.org/10.1086/499374
Campbell A (1961) Conditions for the existence of bacteriophage. Evolution 15:153–165. https://doi.org/10.2307/2406076
Chan BK, Abedon ST, Loc-Carrillo C (2013) Phage cocktails and the future of phage therapy. Future Microbiol 8:769–783. https://doi.org/10.2217/fmb.13.47
Chao L, Levin BR, Stewart FM (1977) A complex community in a simple habitat: an experimental study with bacteria and phage. Ecology 58:369–378. https://doi.org/10.2307/1935611
Chibeu A, Agius L, Gao A, Sabour PM, Kropinski AM, Balamurugan S (2013) Efficacy of bacteriophage LISTEX™P100 combined with chemical antimicrobials in reducing Listeria monocytogenes in cooked turkey and roast beef. Int J Food Microbiol 167:208–214. https://doi.org/10.1016/j.ijfoodmicro.2013.08.018
Choi C, Kuatsjah E, Wu E, Yuan S (2010) The effect of cell size on the burst size of T4 bacteriophage infections of Escherichia coli B23. J Exp Microbiol Immunol 14:85–91
Clark JR, March JB (2006) Bacteriophages and biotechnology: vaccines, gene therapy and antibacterials. Trends Biotechnol 24:212–218. https://doi.org/10.1016/j.tibtech.2006.03.003
Clark DW, Meyer H-P, Leist C, Fiechter A (1986) Effects of growth medium on phage production and induction in Escherichia coli K-12 lambda lysogens. J Biotechnol 3:271–280. https://doi.org/10.1016/0168-1656(86)90009-X
Clokie MRJ, Millard AD, Letarov AV, Heaphy S (2011) Phages in nature. Bacteriophage 1:31–45. https://doi.org/10.4161/bact.1.1.14942
Criscuolo E, Spadini S, Lamanna J, Ferro M, Burioni R (2017) Bacteriophages and their immunological applications against infectious threats. J Immunol Res 2017:1–13. https://doi.org/10.1155/2017/3780697
De Czekala A, Luk D, Bartl P (1972) Large-scale production of lambda bacteriophage and purified lambda deoxyribonucleic acid. Appl Microbiol 23:791–795
Dennehy JJ (2012) What can phages tell us about host-pathogen coevolution? Int J Evol Biol 2012:1–12. https://doi.org/10.1155/2012/396165
d'Herelle F (1917) An invisible microbe that is antagonistic to the dysentery bacillus. C R Acad Sci 165:373–375
Domingo E, Sabo D, Taniguchi T, Weissmann C (1978) Nucleotide sequence heterogeneity of an RNA phage population. Cell 13:735–744
Dunn IJ, Heinzle E, Přenosil JE, Ingham J (1992) Biological reaction engineering : principles, applications and modelling with PC simulation. Wiley-VCH, Weinheim
Egli T (2015) Microbial growth and physiology: a call for better craftsmanship. Front Microbiol 6:287. https://doi.org/10.3389/fmicb.2015.00287
Ellis EL, Delbrück M (1939) The growth of bacteriophage. J Gen Physiol 22:365–384
Fister S, Robben C, Witte AK, Schoder D, Wagner M, Rossmanith P (2016) Influence of environmental factors on phage–bacteria interaction and on the efficacy and infectivity of phage P100. Front Microbiol 7:1152. https://doi.org/10.3389/fmicb.2016.01152
Fong SA, Drilling A, Morales S, Cornet ME, Woodworth BA, Fokkens WJ, Psaltis AJ, Vreugde S, Wormald P-J (2017) Activity of bacteriophages in removing biofilms of Pseudomonas aeruginosa isolates from chronic rhinosinusitis patients. Front Cell Infect Microbiol 7:418. https://doi.org/10.3389/fcimb.2017.00418
Forde SE, Thompson JN, Holt RD, Bohannan BJM (2008) Coevolution drives temporal changes in fitness and diversity across environments in a bacteria-bacteriophage interaction. Evolution 62:1830–1839. https://doi.org/10.1111/j.1558-5646.2008.00411.x
García P, Martínez B, Obeso JM, Rodríguez A (2008) Bacteriophages and their application in food safety. Lett Appl Microbiol 47:479–485. https://doi.org/10.1111/j.1472-765X.2008.02458.x
Gáspár S, Rontó G, Müller G (1979) Determination of the biological parameters of bacterium-phage complexes. Z Allg Mikrobiol 19:163–169
Gáspár S, Módos K, Gy R (1981) Complex method for the determinaton of the physiological parameters of bacterium-phage systems. In: Fedina L, Kanyár B, Kocsis B, Kollai M (eds) Mathematical and Computational methods in Physiology. Pergamon Press, Akadémiai Kiadó, Hungary, pp 141–146
Golec P, Karczewska-Golec J, Łoś M, Węgrzyn G (2014) Bacteriophage T4 can produce progeny virions in extremely slowly growing Escherichia coli host: comparison of a mathematical model with the experimental data. FEMS Microbiol Lett 351:156–161. https://doi.org/10.1111/1574-6968.12372
Grossi GF, Cesareni G, Liello F (1977) Development of phage populations in a bacterial culture: a mathematical model. Z Naturforsch C 32:844–849
Guttman B, Raya R, Kutter E (2005) Basic phage biology. In: Kutter E, Sulakvelidze A (eds) Bacteriophages: biology and applications. CRC Press, Boca Raton, pp 29–66
Hadas H, Einav M, Fishov I, Zaritsky A (1997) Bacteriophage T4 development depends on the physiology of its host Escherichia coli. Microbiology 143:179–185. https://doi.org/10.1099/00221287-143-1-179
Hagens S, Loessner MJ (2007) Application of bacteriophages for detection and control of foodborne pathogens. Appl Microbiol Biotechnol 76:513–519. https://doi.org/10.1007/s00253-007-1031-8
Hagens S, Loessner MJ (2014) Phages of Listeria offer novel tools for diagnostics and biocontrol. Front Microbiol 5:159. https://doi.org/10.3389/fmicb.2014.00159
Haq IU, Chaudhry WN, Akhtar MN, Andleeb S, Qadri I (2012) Bacteriophages and their implications on future biotechnology: a review. Virol J 9:9. https://doi.org/10.1186/1743-422X-9-9
Harrison E, Brockhurst MA (2017) Ecological and evolutionary benefits of temperate phage: what does or doesn’t kill you makes you stronger. BioEssays 39. https://doi.org/10.1002/bies.201700112
Husimi Y (1989) Selection and evolution of bacteriophages in cellstat. Adv Biophys 25:1–43
Husimi Y, Nishigaki K, Kinoshita Y, Tanaka T (1982) Cellstat-a continuous culture system of a bacteriophage for the study of the mutation rate and the selection process of the DNA level. Rev Sci Instrum 53:517–522
Husimi Y, Mori T, Ushijima S, Aita T (1993) Modes of population changeovers in continuous culture of bacterial and viral mutants spectrum. J Theor Biol 165:577–591. https://doi.org/10.1006/jtbi.1993.1208
Hyman P, Abedon ST (2009) Practical methods for determining phage growth parameters. In: Clokie MRJ, Kropinski AM (eds) Bacteriophages: methods and protocols, Vol 1: isolation, characterization, and interactions. Humana Press, pp 175–202
Jacobson H, Jacobson LS (1966) Virustat, a device for continuous production of viruses. Appl Microbiol 14:940–952
Jensen KC, Hair BB, Wienclaw TM, Murdock MH, Hatch JB, Trent AT, White TD, Haskell KJ, Berges BK (2015) Isolation and host range of bacteriophage with lytic activity against methicillin-resistant Staphylococcus aureus and potential use as a fomite decontaminant. PLoS One 10:e0131714. https://doi.org/10.1371/journal.pone.0131714
Jones JB, Jackson LE, Balogh B, Obradovic A, Iriarte FB, Momol MT (2007) Bacteriophages for plant disease control. Annu Rev Phytopathol 45:245–262. https://doi.org/10.1146/annurev.phyto.45.062806.094411
Jungbauer A (2013) Continuous downstream processing of biopharmaceuticals. Trends Biotechnol 31:479–492. https://doi.org/10.1016/j.tibtech.2013.05.011
Kick B, Behler KL, Severin TS, Weuster-Botz D (2017) Chemostat studies of bacteriophage M13 infected Escherichia coli JM109 for continuous ssDNA production. J Biotechnol 258:92–100. https://doi.org/10.1016/j.jbiotec.2017.06.409
Kingwell K (2015) Bacteriophage therapies re-enter clinical trials. Nat Rev Drug Discov 14:515–516. https://doi.org/10.1038/nrd4695
Kiros A, Gashaw T, Teshale A (2016) Phage therapy; a review on the biology and therapeutic application of bacteriophage. ARC J Anim Vet Sci 2:15–25. https://doi.org/10.20431/2455-2518.0204003
Kolesnikova SG, Tulyakova EN, Moiseeva IY (2017) Phage therapy: present and future. J Phys Conf Ser 784:012027. https://doi.org/10.1088/1742-6596/784/1/012027
Kong D, Yin J (1995) Whole-virus vaccine development by continuous culture on a complementing host. Biotechnology (NY) 13:583–558
Koskella B, Brockhurst MA (2014) Bacteria-phage coevolution as a driver of ecological and evolutionary processes in microbial communities. FEMS Microbiol Rev 38:916–931. https://doi.org/10.1111/1574-6976.12072
Kropinski AM, Mazzocco A, Waddell TE, Lingohr E, Johnson RP (2009) Enumeration of bacteriophages by double agar overlay plaque assay. In: Clokie MRJ, Kropinski AM (eds) Bacteriophages: methods and protocols, vol 1: isolation, characterization, and interactions. Humana Press, pp 69–76
Krysiak-Baltyn K, Martin GJO, Stickland AD, Scales PJ, Gras SL (2016) Computational models of populations of bacteria and lytic phage. Crit Rev Microbiol 42:942–968. https://doi.org/10.3109/1040841X.2015.1114466
Krysiak-Baltyn K, Martin GJO, Gras SL (2018) Computational modelling of large scale phage production using a two-stage batch process. Pharmaceuticals (Basel) 11. https://doi.org/10.3390/ph11020031
Kunisaki H, Tanji Y (2010) Intercrossing of phage genomes in a phage cocktail and stable coexistence with Escherichia coli O157:H7 in anaerobic continuous culture. Appl Microbiol Biotechnol 85:1533–1540. https://doi.org/10.1007/s00253-009-2230-2
Kutter E, Kellenberger E, Carlson K, Eddy S, Neitzel J, Messinger L, North J, Guttman B (1994) Effects of bacterial growth conditions and physiology on T4 infection. In: Karam JD (ed) Molecular biology of bacteriophage T4. American Society for Microbiology, Washington, DC, pp 406–418
Labedan B, Legault-Demare J (1974) Evidence for heterogeneity in populations of T5 bacteriophage. J Virol 13:1093–1100
Lenski RE (1988) Dynamics of interactions between bacteria and virulent bacteriophage. In: Marshall KC (ed) Advances in microbial ecology. Plenum Press, New York, pp 1–44. https://doi.org/10.1007/978-1-4684-5409-3_1
Lenski RE, Levin BR (1985) Constraints on the coevolution of bacteria and virulent phage: a model, some experiments, and predictions for natural communities. Am Nat 125:585–602. https://doi.org/10.2307/2461275
Letchumanan V, Chan KG, Pusparajah P, Saokaew S, Duangjai A, Goh BH, Ab Mutalib NS, Lee LH (2016) Insights into bacteriophage application in controlling Vibrio species. Front Microbiol 7:1114. https://doi.org/10.3389/fmicb.2016.01114
Levenspiel O (1999) Chemical reaction engineering, 3rd edn. Wiley, New York
Levin BR, Stewart FM, Chao L (1977) Resource-limited growth, competition, and predation: a model and experimental studies with bacteria and bacteriophage. Am Nat 111:3–24
Lin DM, Koskella B, Lin HC (2017) Phage therapy: an alternative to antibiotics in the age of multi-drug resistence. World J Gastrointest Pharmacol Ther 8:162–173. https://doi.org/10.4292/wjgpt.v8.i3.162
Lindberg HM, Mckean KA, Wang I-N (2014) Phage fitness may help predict phage therapy efficacy. Bacteriophage 4:e964081. https://doi.org/10.4161/21597073.2014.964081
Lindemann BF, Klug C, Schwienhorst A (2002) Evolution of bacteriophage in continuous culture: a model system to test antiviral gene therapies for the emergence of phage escape mutants. J Virol 76:5784–5792. https://doi.org/10.1128/JVI.76.11.5784-5792.2002
Lotka AJ (1925) Elements of physical biology. Williams and Wilkins, Baltimore
Ly-Chatain MH (2014) The factors affecting effectiveness of treatment in phages therapy. Front Microbiol 5. https://doi.org/10.3389/fmicb.2014.00051
Mancuso F, Shi J, Malik D (2018) High throughput manufacturing of bacteriophages using continuous stirred tank bioreactors connected in series to ensure optimum host bacteria physiology for phage production. Viruses 10:537. https://doi.org/10.3390/v10100537
Marks T, Sharp R (2000) Bacteriophages and biotechnology: a review. J Chem Technol Biotechnol 75:6–17. https://doi.org/10.1002/(SICI)1097-4660(200001)75:1<6::AID-JCTB157>3.0.CO;2-A
Matsuzaki S, Rashel M, Uchiyama J, Sakurai S, Ujihara T, Kuroda M, Imai S, Ikeuchi M, Tani T, Fujieda M, Wakiguchi H (2005) Bacteriophage therapy: a revitalized therapy against bacterial infectious diseases. J Infect Chemother 11:211–219. https://doi.org/10.1007/s10156-005-0408-9
Merabishvili M, Pirnay JP, Verbeken G, Chanishvili N, Tediashvili M, Lashkhi N, Glonti T, Krylov V, Mast J, Van Parys L, Lavigne R, Volckaert G, Mattheus W, Verween G, De Corte P, Rose T, Jennes S, Zizi M, De Vos D, Vaneechoutte M (2009) Quality-controlled small-scale production of a well-defined bacteriophage cocktail for use in human clinical trials. PLoS One 4:e4944. https://doi.org/10.1371/journal.pone.0004944
Mizoguchi K, Morita M, Fischer CR, Yoichi M, Tanji Y, Unno H (2003) Coevolution of bacteriophage PP01 and Escherichia coli O157:H7 in continuous culture. Appl Environ Microbiol 69:170–176. https://doi.org/10.1128/AEM.69.1.170-176.2003
Mojica KDA, Brussaard CPD (2014) Factors affecting virus dynamics and microbial host - virus interactions in marine environments. FEMS Microbiol Ecol 89:495–515. https://doi.org/10.1111/1574-6941.12343
Monk AB, Rees CD, Barrow P, Hagens S, Harper DR (2010) Bacteriophage applications: where are we now? Lett Appl Microbiol 51:363–369. https://doi.org/10.1111/j.1472-765X.2010.02916.x
Nabergoj D, Kuzmić N, Drakslar B, Podgornik A (2018a) Effect of dilution rate on productivity of continuous bacteriophage production in cellstat. Appl Microbiol Biotechnol 102:3649–3661. https://doi.org/10.1007/s00253-018-8893-9
Nabergoj D, Modic P, Podgornik A (2018b) Effect of bacterial growth rate on bacteriophage population growth rate. Microbiologyopen 7:e00558. https://doi.org/10.1002/mbo3.558
Northrop JH (1938) Concentration and purification of bacteriophage. J Gen Physiol 21:335–366
Novick A, Szilard L (1950) Experiments with the chemostat on spontaneous mutations of bacteria. Proc Natl Acad Sci U S A 36:708–719
Pherecydes Pharma (2018) https://www.pherecydes-pharma.com/. Accessed 28 June 2018
Podgornik A, Janež N, Smrekar F, Peterka M (2014) Continuous production of bacteriophages. In: Subramanian G (ed) Continuous processing in pharmaceutical manufacturing. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp 297–338
Rathore AS (2015) Continuous processing for production of biotech therapeutics. PDA J Pharm Sci Technol 69:333. https://doi.org/10.5731/pdajpst.2015.01072
Roach DR, Debarbieux L (2017) Phage therapy: awakening a sleeping giant. Emerg Top Life Sci 1:93–103. https://doi.org/10.1042/ETLS20170002
Ross A, Ward S, Hyman P (2016) More is better: selecting for broad host range bacteriophages. Front Microbiol 7:1352. https://doi.org/10.3389/fmicb.2016.01352
Roy B, Philippe C, Loessner M, Goulet J, Moineau S (2018) Production of bacteriophages by Listeria cells entrapped in organic polymers. Viruses 10:324. https://doi.org/10.3390/v10060324
Santos SB, Carvalho C, Azeredo J, Ferreira EC (2014) Population dynamics of a Salmonella lytic phage and its host: implications of the host bacterial growth rate in modelling. PLoS One 9:e102507. https://doi.org/10.1371/journal.pone.0102507
Sargeant K (1969) The deep culture of bacteriophage. In: Norris JR, Ribbons DW (eds) Methods in microbiology, vol 1. Academic Press, London, pp 505–520
Sauvageau D, Cooper DG (2010) Two-stage, self-cycling process for the production of bacteriophages. Microb Cell Factories 9:81. https://doi.org/10.1186/1475-2859-9-81
Schofield DA, Sharp NJ, Westwater C (2012) Phage-based platforms for the clinical detection of human bacterial pathogens. Bacteriophage 2:105–283. https://doi.org/10.4161/bact.19274
Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, Barr JJ, Reed SL, Rohwer F, Benler S, Segall AM, Taplitz R, Smith DM, Kerr K, Kumaraswamy M, Nizet V, Lin L, McCauley MD, Strathdee SA, Benson CA, Pope RK, Leroux BM, Picel AC, Mateczun AJ, Cilwa KE, Regeimbal JM, Estrella LA, Wolfe DM, Henry MS, Quinones J, Salka S, Bishop-Lilly KA, Young R, Hamilton T (2017) Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother 61:e00954–e00917. https://doi.org/10.1128/AAC.00954-17
Schwienhorst A, Lindemann BF, Eigen M (1996) Growth kinetics of a bacteriophage in continuous culture. Biotechnol Bioeng 50:217–221. https://doi.org/10.1002/bit.260500204
Shao Y, Wang I-N (2008) Bacteriophage adsorption rate and optimal lysis time. Genetics 180:471–482. https://doi.org/10.1534/genetics.108.090100
Sharma S, Chatterjee S, Datta S, Prasad R, Dubey D, Prasad RK, Vairale MG (2017) Bacteriophages and its applications:an overview. Folia Microbiol (Praha) 62:17–55. https://doi.org/10.1007/s12223-016-0471-x
Smrekar F, Ciringer M, Peterka M, Podgornik A, Strancar A (2008) Purification and concentration of bacteriophage T4 using monolithic chromatographic supports. J Chromatogr B Analyt Technol Biomed Life Sci 861:177–180. https://doi.org/10.1016/j.jchromb.2007.05.048
Spanakis E, Horne MT (1987) Co-adaptation of Escherichia coli and Coliphage λvir in continuous culture. J Gen Microbiol 133:353–360. https://doi.org/10.1099/00221287-133-2-353
Storms ZJ, Sauvageau D (2014) Evidence that the heterogeneity of a T4 population is the result of heritable traits. PLoS One 9:e116235. https://doi.org/10.1371/journal.pone.0116235
Storms ZJ, Sauvageau D (2015) Modeling tailed bacteriophage adsorption: insight into mechanisms. Virology 485:355–362. https://doi.org/10.1016/j.virol.2015.08.007
Storms ZJ, Arsenault E, Sauvageau D, Cooper DG (2010) Bacteriophage adsorption efficiency and its effect on amplification. Bioprocess Biosyst Eng 33:823–831. https://doi.org/10.1007/s00449-009-0405-y
Storms ZJ, Brown T, Cooper DG, Sauvageau D, Leask RL (2013) Impact of the cell life-cycle on bacteriophage T4 infection. FEMS Microbiol Lett 353:63–68. https://doi.org/10.1111/1574-6968.12402
Summers WC (2012) The strange history of phage therapy. Bacteriophage 2:130–133. https://doi.org/10.4161/bact.20757
Taj MK, Ji X, Taj I, Hussani TM, Samreen Z, Wei Y (2013) Different phase Escherichia coli effect on T4 bacteriophage lysis and production. Int J Appl Nat Sci 2:73–76
Tucker RG (1961) The role of magnesium ions in the growth of Salmonella phage anti-R. J Gen Microbiol 26:313–323. https://doi.org/10.1099/00221287-26-2-313
Twort FW (1915) An investigation on the nature of ultra-microscopic viruses. Lancet 186:1241–1243. https://doi.org/10.1016/S0140-6736(01)20383-3
Varon M (1979) Selection of predation-resistant bacteria in continuous culture. Nature 277:386–388. https://doi.org/10.1038/277386a0
Volterra V (1926) Fluctuations in the abundance of a species considered mathematically. Nature 118:558–560
Wang IN (2006) Lysis timing and bacteriophage fitness. Genetics 172:17–26. https://doi.org/10.1534/genetics.105.045922
Warner CM, Barker N, Lee S-W, Perkins EJ (2014) M13 bacteriophage production for large-scale applications. Bioprocess Biosyst Eng 37:2067–2072. https://doi.org/10.1007/s00449-014-1184-7
Weitz JS, Hartman H, Levin SA (2005) Coevolutionary arms races between bacteria and bacteriophage. PNAS 102:9535–9540. https://doi.org/10.1073/pnas.0504062102
Wittebole X, De Roock S, Opal SM (2014) A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens. Virulence 5:226–235. https://doi.org/10.4161/viru.25991
Wright A, Hawkins CH, Änggård EE, Harper DR (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 34:349–357. https://doi.org/10.1111/j.1749-4486.2009.01973.x
Yosef I, Kiro R, Molshanski-Mor S, Edgar R, Qimron U (2014) Different approaches for using bacteriophages against antibiotic-resistant bacteria. Bacteriophage 4:e28491. https://doi.org/10.4161/bact.28491
You L, Suthers PF, Yin J (2002) Effects of Escherichia coli physiology on growth of phage T7 in vivo and in silico. J Bacteriol 184:1888–1894. https://doi.org/10.1128/JB.184.7.1888-1894.2002
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The study was funded by the European Regional Development Fund and Slovenian Ministry of Education, Science and Sport (project BioPharm.Si).
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Jurač, K., Nabergoj, D. & Podgornik, A. Bacteriophage production processes. Appl Microbiol Biotechnol 103, 685–694 (2019). https://doi.org/10.1007/s00253-018-9527-y
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DOI: https://doi.org/10.1007/s00253-018-9527-y