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Selection of phages and conditions for the safe phage therapy against Pseudomonas aeruginosa infections

  • Research Article
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Virologica Sinica

Abstract

The emergence of multidrug-resistant bacterial pathogens forced us to consider the phage therapy as one of the possible alternative approaches to treatment. The purpose of this paper is to consider the conditions for the safe, long-term use of phage therapy against various infections caused by Pseudomonas aeruginosa. We describe the selection of the most suitable phages, their most effective combinations and some approaches for the rapid recognition of phages unsuitable for use in therapy. The benefits and disadvantages of the various different approaches to the preparation of phage mixtures are considered, together with the specific conditions that are required for the safe application of phage therapy in general hospitals and the possibilities for the development of personalized phage therapy.

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References

  • Abedon ST, Kuhl SJ, Blasdel BG, Kutter EM. 2011. Phage treatment of human infections. Bacteriophage, 1: 66–85.

    Article  PubMed Central  PubMed  Google Scholar 

  • Alemayehu D, Casey PG, McAuliffe O, Guinane CM, Martin JG, Shanahan F, Coffey A, Ross RP, Hill C. 2012. Bacteriophages φMR299-2 and φNH-4 can eliminate Pseudomonas aeruginosa in the murine lung and on cystic fibrosis lung airway cells. MBio, 3: e00029–e00012.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Briers Y, Walmagh M, Grymonprez B, Biebl M, Pirnay JP, Defraine V, Michiels J, Cenens W, Aertsen A, Miller S, Lavigne R. 2014. Art-175 is a highly efficient antibacterial against multidrug-resistant strains and persisters of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 58: 3774–3784.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Burkal’tseva MV, Pleteneva EA, Shaburova OV, Kadykov VA, Krylov VN. 2006. Genome conservatism of phiKMV-like bacteriophages (T7 supergroup) active against Pseudomonas aeruginosa. Genetika, 42: 33–38. (In Russian)

    PubMed  Google Scholar 

  • Castillo FJ, Bartell PF. 1974. Studies on the bacteriophage 2 receptors of Pseudomonas aeruginosa. J Virol, 14: 904–909.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Castillo FJ, Bartell PF. 1976. Localization and functional role of the pseudomonas bacteriophage 2 depolymerase. J Virol, 18:701–708.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ceyssens PJ, Hertveldt K, Ackermann HW, Noben JP, Demeke M, Volckaert G, Lavigne R. 2008. The intron-containing genome of the lytic Pseudomonas phage LUZ24 resembles the temperate phage PaP3. Virology, 377: 233–238.

    Article  CAS  PubMed  Google Scholar 

  • Ceyssens PJ, Miroshnikov K, Mattheus W, Krylov V, Robben J, Noben JP, Vanderschraeghe S, Sykilinda N, Kropinski AM, Volckaert G, Mesyanzhinov V, Lavigne R. 2009. Comparative analysis of the widespread and conserved PB1-like viruses infecting Pseudomonas aeruginosa. Environ Microbiol, 11: 2874–2883.

    Article  CAS  PubMed  Google Scholar 

  • Ceyssens PJ, Glonti T, Kropinski NM, Lavigne R, Chanishvili N, Kulakov L, Lashkhi N, Tediashvili M, Merabishvili M. 2011. Phenotypic and genotypic variations within a single bacteriophage species. Virol J, 8: 134.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ceyssens PJ, Minakhin L, Van den Bossche A, Yakunina M, Klimuk E, Blasdel B, De Smet J, Noben JP, Bläsi U, Severinov K, Lavigne R. 2014. Development of giant bacteriophage ΦKZ is independent of the host transcription apparatus. J Virol, 88:10501–10510.

    Article  CAS  PubMed  Google Scholar 

  • Chaconas G, de Bruijn FJ, Casadaban MJ, Lupski JR, Kwoh TJ, Harshey RM, DuBow MS, Bukhari AI. 1981. In vitro and in vivo manipulations of bacteriophage Mu DNA: cloning of Mu ends and construction of mini-Mu’s carrying selectable markers. Gene, 13: 37–46.

    Article  CAS  PubMed  Google Scholar 

  • Chanishvili N. 2012. Phage therapy-history from Twort and d’Herelle through Soviet experience to current approaches. Adv Virus Res, 83: 3–40.

    Article  CAS  PubMed  Google Scholar 

  • Cornelissen A, Hardies SC, Shaburova OV, Krylov VN, Mattheus W, Kropinski AM, Lavigne R. 2012. Complete genome sequence of the giant virus OBP and comparative genome analysis of the diverse ΦKZ-related phages. J Virol, 86: 1844–1852.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Duckworth DH. 1976. “Who discovered bacteriophage?” Bacteriol Rev, 40: 793–802.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Eller MR, Vidigal PM, Salgado RL, Alves MP, Dias RS, da Silva CC, de Carvalho AF, Kropinski A, De Paula SO. 2014. UFV-P2 as a member of the LUZ24likevirus genus: a new overview on comparative functional genome analyses of the LUZ24-like phages. BMC Genomics, 15: 7.

    Article  PubMed Central  PubMed  Google Scholar 

  • Fehér T, Karcagi I, Blattner FR, Pósfai G. 2012, Bacteriophage recombineering in the lytic state using the lambda red recombinases. Microb Biotechnol, 5: 466–476.

    Article  PubMed Central  PubMed  Google Scholar 

  • Fortier LC Sekulovic O. 2013. Importance of prophages to evolution and virulence of bacterial pathogens. Virulence, 4: 354–365.

    Article  PubMed Central  PubMed  Google Scholar 

  • Glonti T, Chanishvili N, Taylor PW. 2010. Bacteriophage-derived enzyme that depolymerizes the alginic acid capsule associated with cystic fibrosis isolates of Pseudomonas aeruginosa. J Appl Microbiol, 108: 695–702.

    Article  CAS  PubMed  Google Scholar 

  • Glukhov AS, Krutilina AI, Shlyapnikov MG, Severinov K, Lavysh D, Kochetkov VV, McGrath JW, de Leeuwe C, Shaburova OV, Krylov VN, Akulenko NV, Kulakov LA. 2012. Genomic analysis of Pseudomonas putida phage tf with localized single-strand DNA interruptions. PLoS One, 7: e51163.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Górski A, Miedzybrodzki R, Borysowski J, Weber-Dabrowska B, Lobocka M, Fortuna W, Letkiewicz S, Zimecki M, Filby G. 2009. Bacteriophage therapy for the treatment of infections. Curr Opin Investig Drugs, 10: 766–774.

    PubMed  Google Scholar 

  • Groisman EA, Casadaban MJ. 1987. Cloning of genes from members of the family Enterobacteriaceae with mini-Mu bacteriophage containing plasmid replicons. J Bacteriol, 169: 687–693.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hanlon GW, Denyer SP, Olliff CJ, Ibrahim LJ. 2001. Reduction in exopolysaccharide viscosity as an aid to bacteriophage penetration through Pseudomonas aeruginosa biofilms. Appl Environ Microbiol, 67: 2746–2753.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Henry M, Lavigne R, Debarbieux L. 2013. Predicting in vivo efficacy of therapeutic bacteriophages used to treat pulmonary infections. Antimicrob Agents Chemother, 57: 5961–5968.

    Article  PubMed Central  PubMed  Google Scholar 

  • d’Herelle FH. 1917. Sur un microbe invisible antagoniste des bacilles dysenteriques. C R Acad Sci, 165: 373–375. (In French)

    Google Scholar 

  • Hertveldt K, Lavigne R, Pleteneva E, Sernova N, Kurochkina L, Korchevskii R, Robben J, Mesyanzhinov V, Krylov VN, Volckaert G. 2005. Genome comparison of Pseudomonas aeruginosa large phages. J Mol Biol, 2; 354: 536–545.

    Article  Google Scholar 

  • Holloway BW, Egan JB, Monk M. 1960. Lysogeny in Pseudomonas aeruginosa. Aust J Exp Biol Med Sci. 38: 321–329.

    Article  CAS  PubMed  Google Scholar 

  • James CE, Fothergill JL, Kalwij H, Hall AJ, Cottell J, Brockhurst MA, Winstanley C. 2012. Differential infection properties of three inducible prophages from an epidemic strain of Pseudomonas aeruginosa. BMC Microbiol, 12: 216.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jarrell K, Kropinski AM. 1977. Identification of the cell wall receptor for bacteriophage E79 in Pseudomonas aeruginosa strain PAO. J Virol, 23: 461–466.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jenkins FJ, Casadaban MJ, Roizman B. 1985. Application of the mini-Mu-phage for target-sequence-specific insertional mutagenesis of the herpes simplex virus genome. Proc Natl Acad Sci U S A, 82: 4773–4777.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jeon J, Kim JW, Yong D, Lee K, Chong Y. 2012. Complete genome sequence of the bacteriophage YMC01/01/P52 PAE BP, which causeslysis of verona integron-encoded metallo-β-lactamase-producing,carbapenem-resistant Pseudomonas aeruginosa. J Virol, 86: 13876–13877

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kaplan AM, Akhverdian VZ, Reulets MA, Krylov VN. 1988. Compatibility of transposable phages of Escherichia coli and Pseudomonas aeruginosa. I. Co-development of phages Mu and D3112 and integration of phage D3112 into RP4::Mu plasmid in Pseudomonas aeruginosa cells. Genetika, 24: 634–640. (In Russian)

    CAS  PubMed  Google Scholar 

  • Kim S, Rahman M, Kim J. 2012. Complete genome sequence of Pseudomonas aeruginosa lytic bacteriophage PA1O which resembles temperate bacteriophage D3112. J Virol, 86: 3400–3401.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kulakov LA, Ksenzenko VN, Shlyapnikov MG, Kochetkov VV, Del Casale A, Allen CC, Larkin MJ, Ceyssens PJ, Lavigne R. 2009. Genomes of “phiKMV-like viruses” of Pseudomonas aeruginosa contain localized single-strand interruptions. Virology, 391: 1–4.

    Article  CAS  PubMed  Google Scholar 

  • Krylov VN, Shaburova OV. 2012. Factors Favoring Co-Evolution of Pseudomonas Aeruginosa and its Viruses in Microbial Communities of Infected Wounds Surfaces and Prospects for Phage Therapy. In: Pseudomonas Aeruginosa: Symptoms of Infection, Antibiotic Resistance and Treatment. Beningo M. Penha Escudeiro and Eduardo C. Baracho Marques. USA: NOVA Science Publishers. pp37–66.

    Google Scholar 

  • Krylov VN, Zhazykov IZh. 1978. Pseudomonas bacteriophage phiKZ-possible model for studying the genetic control of morphogenesis. Genetika, 14: 678–685. (In Russian)

    CAS  PubMed  Google Scholar 

  • Krylov VN, Smirnova TA, Minenkova IB, Plotnikova TG, Zhazikov IZ, Khrenova EA. 1984. Pseudomonas bacteriophage phi KZ contains an inner body in its capsid. Can J Microbiol, 30: 758–762.

    Article  CAS  PubMed  Google Scholar 

  • Krylov V, Shaburova O, Krylov S and Pleteneva E. 2013. A Genetic Approach to the Development of New Therapeutic Phages to Fight Pseudomonas aeruginosa in Wound Infections. Viruses, 5:15–53.

    Article  PubMed Central  Google Scholar 

  • Krylov V, Pleteneva E, Shaburova O, Bourkaltseva M, Krylov S, Chesnokova E, Polygach O.Common Preconditions for Safe Phage Therapy of Pseudomonas aeruginosa Infections. 2014. Advances in Microbiology, 4: 766–773.

    Article  Google Scholar 

  • Krylov SV, Pleteneva EA, Burkal’tseva MV, Shaburova OV, Miroshnikov KA, Lavigne R, Cornelissen A, Krylov VN. 2011. Genome instability of Pseudomonas aeruginosa phages of the EL species: examination of virulent mutants. Genetika, 47:183–189. (In Russian)

    CAS  PubMed  Google Scholar 

  • Kutter E, De Vos D, Gvasalia G, Alavidze Z, Gogokhia L, Kuhl S, Abedon ST. 2010. Phage therapy in clinical practice: treatment of human infections. Curr Pharm Biotechnol, 11: 69–86.

    Article  CAS  PubMed  Google Scholar 

  • Lavigne R, Burkaltseva MV, Robben J, Sykilinda NN, Kurochkina LP, Grymomprez B, Jonckx B, Krylov VN, Mesyanzhinov VV, Volckaert G. 2003. The genome of bacteriophage phiKMV, a T7-like virus infecting Pseudomonas aeruginosa. Virology, 312:49–59.

    Article  CAS  PubMed  Google Scholar 

  • Lindberg RB, Latta RL. 1974. Phage typing of Pseudomonas aeruginosa:clinical and epidemiologic considerations. J Infect Dis. 130: S33–S42.

    Article  PubMed  Google Scholar 

  • Lu S, Le S, Tan Y, Zhu J, Li M, Rao X, Zou L, Li S, Wang J, Jin X, Huang G, Zhang L, Zhao X, Hu F. 2013. Genomic and proteomic analyses of the terminally redundant genome of the Pseudomonas aeruginosa phage PaP1: establishment of genus PaP1-like phages. PLoS One, 8: e62933.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marinelli LJ, Hatfull GF, Piuri M. 2012. Recombineering: A powerful tool for modification of bacteriophage genomes. Bacteriophage, 2: 5–14.

    Article  PubMed Central  PubMed  Google Scholar 

  • Maura D, Debarbieux L. 2011. Bacteriophages as twenty-first century antibacterial tools for food and medicine. Appl Microbiol Biotechnol, 90: 851–859.

    Article  CAS  PubMed  Google Scholar 

  • McCallin S, Alam Sarker S, Barretto C, Sultana S, Berger B, Huq S, Krause L, Bibiloni R, Schmitt B, Reuteler G, Brüssow H. 2013. Safety analysis of a Russian phage cocktail: from metagenomic analysis to oral application in healthy human subjects. Virology, 443: 187–196.

    Article  CAS  PubMed  Google Scholar 

  • Mesyanzhinov VV, Robben J, Grymonprez B, Kostyuchenko VA, Bourkaltseva MV, Sykilinda NN, Krylov VN, Volckaert G. 2002. The Genome of Bacteriophage phiKZ of Pseudomonas aeruginosa. J Mol Biol, 317: 1–19.

    Article  CAS  PubMed  Google Scholar 

  • Miao EA, Miller SI. 1999. Bacteriophages in the evolution of pathogen-host interactions. Proc Natl Acad Sci U S A, 96:9452–9454.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Morello E, Saussereau E, Maura D, Huerre M, Touqui L, Debarbieux L. 2011. Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention. PLoS One, 6: e16963.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Murray NE. 2006. The impact of phage lambda: from restriction to recombineering. Biochem Soc Trans, 34: 203–207.

    Article  CAS  PubMed  Google Scholar 

  • Perepanova TS, Darbeeva OS, Kotliarova GA, Kondrat’eva EM, Maĭskaia LM, Malysheva VF, Baĭguzina FA, Grishkova NV. 1995. The efficacy of bacteriophage preparations in treating in-flammatory urologic diseases. Urol Nefrol (Mosk), 5: 14–17. (In Russian)

    Google Scholar 

  • Pleteneva EA, Shaburova OV, Sykilinda NN, Miroshnikov KA, Krylov SV, Mesianzhinov VV, Krylov VN. 2008. Study of the diversity in a group of phages of Pseudomonas aeruginosa species PB1 (Myoviridae) and their behavior in adsorbtion-resistant bacterial mutants. Genetika, 44: 185–194. (In Russian)

    CAS  PubMed  Google Scholar 

  • Pleteneva EA, Shaburova OV, Krylov VN. 2009. A formal scheme of adsorptional receptors in Pseudomonas aeruginosa and possibilities for its practical implementation. Genetika, 45: 43–49. (In Russian)

    CAS  PubMed  Google Scholar 

  • Pleteneva EA, Krylov SV, Shaburova OV, Burkal’tseva MV, Miroshnikov KA, Krylov VN. 2010. Pseudolysogeny of Pseudomonas aeruginosa bacteria infected with phiKZ-like bacteriophages. Genetika, 46: 26–32. (In Russian)

    Google Scholar 

  • Pleteneva EA, Burkal’tseva MV, Shaburova OV, Krylov SV, Pechnikova EV, Sokolova OS, Krylov VN. 2011. TL, the new bacteriophage of Pseudomonas aeruginosa and its application for the search of halo-producing bacteriophages. Genetika, 47: 5–9. (In Russian)

    CAS  PubMed  Google Scholar 

  • Plotnikova TG, Kulakov LA, Eremenko EN, Fedorova TV, Krylov VN. 1982. Expression of the genome of Mu-like phage D3112 specific for Pseudomonas aeruginosa in Escherichia coli and Pseudomonas putida cells. Genetika, 18: 1075–1084. (In Russian)

    CAS  PubMed  Google Scholar 

  • Plotnikova TG, Ianenko AS, Kirsanov NB, Krylov VN. 1983. Transposition of the phage D3112 genome in Escherichia coli cells. Genetika, 19: 1611–1915. (In Russian)

    CAS  PubMed  Google Scholar 

  • Rodríguez-Rubio L, Martínez B, Donovan DM, Rodríguez A, García P. 2012. Bacteriophage virion-associated peptidoglycan hydrolases: potential new enzybiotics. Critical Reviews in Microbiology, 39: 427–434.

    Article  PubMed  Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T, 1989. Molecular Cloning: A Laboratory Manual. Second edition. New York: Cold Spring Harbor Press. V.3, Apendix A.1-4

    Google Scholar 

  • Schmelcher M, Tchang VS, Loessner MJ. 2011. Domain shuffling and module engineering of Listeria phage endolysins for enhanced lytic activity and binding affinity. Microb Biotechnol, 4:651–662.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schmelcher M, Donovan DM, Loessner MJ. 2012. Bacteriophage endolysins as novel antimicrobials. Future Microbiol, 7: 1147–1171.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Seeger K, Saunders D, Harris D, Parkhill J, Hancock RE, Brinkman FS, Levesque RC. 2009. Newly introduced genomic prophage islands are critical determinants of in vivo competitiveness in the Liverpool Epidemic Strain of Pseudomonas aeruginosa. Genome Res, 19: 12–23.

    PubMed Central  PubMed  Google Scholar 

  • Sokolova OS, Shaburova OV, Pechnikova EV, Shaytan AK, Krylov SV, Kiselev NA, Krylov VN. 2014. Genome packaging in EL and Lin68, two giant phiKZ-like bacteriophages of P. aeruginosa. Virology, 468–470: 472–478.

    Article  PubMed  Google Scholar 

  • Tan Y, Zhang K, Rao X, Jin X, Huang J, Zhu J, Chen Z, Hu X, Shen X, Wang L, Hu F. 2007. Whole genome sequencing of a novel temperate bacteriophage of P. aeruginosa: evidence of tRNA gene mediating integration of the phage genome into the hostbacterial chromosome. Cell Microbiol, 9: 479–491.

    Article  CAS  PubMed  Google Scholar 

  • Thomas JA, Rolando MR, Carroll CA, Shen PS, Belnap DM, Weintraub ST, Serwer P, Hardies SC. 2008. Characterization of Pseudomonas chlororaphis myovirus 201varphi2-1 via genomic sequencing, mass spectrometry, and electron microscopy. Virology, 376: 330–338.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Thomason LC, Oppenheim AB, Court DL. 2009. Modifying bacteriophage lambda with recombineering. Methods Mol Biol, 501:239–251.

    Article  CAS  PubMed  Google Scholar 

  • Twort FW. 1915. An investigation on the nature of ultra-microscopic viruses. Lancet, ii: 1241–1243.

    Article  Google Scholar 

  • Winstanley C, Langille MG, Fothergill JL, Kukavica-Ibrulj I, Paradis-Bleau C, Sanschagrin F, Thomson NR, Winsor GL, Quail MA, Lennard N, Bignell A, Clarke L, Seeger K, Saunders D, Harris D, Parkhill J, Hancock RE, Brinkman FS, Levesque RC. 2009. Newly introduced genomic prophage islands are critical determinants of in vivo competitiveness in the Liverpool Epidemic Strain of Pseudomonas aeruginosa. Genome Res, 19:12–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wright A, Hawkins CH, Anggård 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.

    Article  CAS  PubMed  Google Scholar 

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  1. I.I. Mechnikov Research Institute for Vaccines & Sera, RAMS, Moscow, 105064, Russian

    Victor Krylov, Olga Shaburova, Elena Pleteneva, Sergey Krylov, Alla Kaplan, Maria Burkaltseva, Olga Polygach & Elena Chesnokova

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  1. Victor Krylov
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  2. Olga Shaburova
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  3. Elena Pleteneva
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  4. Sergey Krylov
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  6. Maria Burkaltseva
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  7. Olga Polygach
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  8. Elena Chesnokova
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Correspondence to Victor Krylov.

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Krylov, V., Shaburova, O., Pleteneva, E. et al. Selection of phages and conditions for the safe phage therapy against Pseudomonas aeruginosa infections. Virol. Sin. 30, 33–44 (2015). https://doi.org/10.1007/s12250-014-3546-3

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