The Citizen Phage Library: Rapid Isolation of Phages for the Treatment of Antibiotic Resistant Infections in the UK.

Julie Fletcher, Robyn Manley, Christian Fitch, Christina Bugert, Karen Moore, Audrey Farbos, Michelle Michelsen, Shayma Alathari, Nicola Senior, Alice Mills, Natalie Whitehead, James Soothill, Stephen Michell, Ben Temperton
Author Information
  1. Julie Fletcher: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK. ORCID
  2. Robyn Manley: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK. ORCID
  3. Christian Fitch: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK. ORCID
  4. Christina Bugert: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
  5. Karen Moore: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK. ORCID
  6. Audrey Farbos: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
  7. Michelle Michelsen: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
  8. Shayma Alathari: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK. ORCID
  9. Nicola Senior: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK. ORCID
  10. Alice Mills: Exeter Science Centre, Kaleider Studios, 45 Preston Street, Exeter EX1 1DF, UK.
  11. Natalie Whitehead: Exeter Science Centre, Kaleider Studios, 45 Preston Street, Exeter EX1 1DF, UK. ORCID
  12. James Soothill: Microbiology, Virology and Infection Control, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH, UK.
  13. Stephen Michell: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK. ORCID
  14. Ben Temperton: Biosciences, Faculty of Health and Life Sciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK. ORCID

Abstract

Antimicrobial resistance poses one of the greatest threats to global health and there is an urgent need for new therapeutic options. Phages are viruses that infect and kill bacteria and phage therapy could provide a valuable tool for the treatment of multidrug-resistant infections. In this study, water samples collected by citizen scientists as part of the Citizen Phage Library (CPL) project, and wastewater samples from the Environment Agency yielded phages with activity against clinical strains BPRG1484 and BPRG1482. A total of 169 and 163 phages were found for and , respectively, within four days of receiving the strains. A third strain ( BPRG1486) demonstrated cross-reactivity with 42 phages already held in the CPL collection. Seed lots were prepared for four phages and a cocktail combining these phages was found to reduce melanisation in a infection model. The resources and protocols utilised by the Citizen Phage Library enabled the rapid isolation and characterisation of phages targeted against multiple strains. In the future, within a clearly defined regulatory framework, phage therapy could be made available on a named-patient basis within the UK.

Keywords

References

  1. Pharmaceuticals (Basel). 2021 Oct 03;14(10): [PMID: 34681243]
  2. Lancet. 2022 Feb 12;399(10325):629-655 [PMID: 35065702]
  3. Methods Mol Biol. 2009;501:81-5 [PMID: 19066813]
  4. Bioinformatics. 2023 Jan 1;39(1): [PMID: 36453861]
  5. Phage (New Rochelle). 2020 Mar 1;1(1):27-36 [PMID: 36147620]
  6. Microbiome. 2021 Apr 14;9(1):92 [PMID: 33853672]
  7. Front Microbiol. 2019 Jul 23;10:1674 [PMID: 31396188]
  8. iScience. 2022 Mar 19;25(4):104121 [PMID: 35402883]
  9. Clin Microbiol Infect. 2022 Jan;28(1):145-146 [PMID: 34619394]
  10. J Biomed Sci. 2022 Mar 30;29(1):23 [PMID: 35354477]
  11. Curr Opin Virol. 2022 Feb;52:24-29 [PMID: 34801778]
  12. Viruses. 2023 Mar 10;15(3): [PMID: 36992430]
  13. Front Med (Lausanne). 2023 May 17;10:1088494 [PMID: 37265479]
  14. Microb Cell Fact. 2015 Apr 16;14:57 [PMID: 25890161]
  15. Open Forum Infect Dis. 2020 Aug 27;7(9):ofaa389 [PMID: 33005701]
  16. mBio. 2020 Aug 4;11(4): [PMID: 32753497]
  17. EClinicalMedicine. 2021 Nov 24;41:101221 [PMID: 34877512]
  18. Front Microbiol. 2021 Mar 29;12:613529 [PMID: 33868187]
  19. Nucleic Acids Res. 2020 Jan 8;48(D1):D517-D525 [PMID: 31665441]
  20. Viruses. 2021 Jun 29;13(7): [PMID: 34209836]
  21. Viruses. 2022 Jul 07;14(7): [PMID: 35891470]
  22. Antibiotics (Basel). 2022 Jun 22;11(7): [PMID: 35884092]
  23. Microbiology (Reading). 2009 May;155(Pt 5):1516-1522 [PMID: 19383703]
  24. Viruses. 2021 Mar 18;13(3): [PMID: 33803862]
  25. Clin Infect Dis. 2023 Jan 6;76(1):103-112 [PMID: 35676823]
  26. Nat Rev Microbiol. 2023 Oct;21(10):686-700 [PMID: 37460672]
  27. Viruses. 2021 Oct 12;13(10): [PMID: 34696479]
  28. Clin Infect Dis. 2023 Oct 13;77(8):1079-1091 [PMID: 37279523]
  29. Viruses. 2020 Nov 06;12(11): [PMID: 33172115]
  30. Nat Chem Biol. 2023 Nov;19(11):1342-1350 [PMID: 37231267]
  31. Curr Opin Virol. 2022 Apr;53:101209 [PMID: 35240424]
  32. Bioinformatics. 2017 Aug 01;33(15):2379-2380 [PMID: 28379287]
  33. Nat Commun. 2022 Jan 18;13(1):302 [PMID: 35042848]
  34. Future Sci OA. 2020 May 06;6(6):FSO477 [PMID: 32670605]
  35. Viruses. 2022 Feb 08;14(2): [PMID: 35215934]
  36. Annu Rev Virol. 2023 Sep 29;10(1):503-524 [PMID: 37268007]
  37. Sci Rep. 2023 Oct 24;13(1):18204 [PMID: 37875544]
  38. Viruses. 2021 May 08;13(5): [PMID: 34066841]
  39. Curr Opin Virol. 2022 Feb;52:236-243 [PMID: 34971929]
  40. Med Res Rev. 2019 Sep;39(5):2000-2025 [PMID: 30887551]
  41. Phage (New Rochelle). 2021 Dec 1;2(4):214-223 [PMID: 36159887]
  42. Clin Ther. 2023 Aug;45(8):797-801 [PMID: 37442654]
  43. Pharm Res. 2015 Jul;32(7):2173-9 [PMID: 25585954]
  44. Nat Commun. 2022 Jul 22;13(1):4239 [PMID: 35869081]
  45. Bacteriophage. 2011 Mar;1(2):66-85 [PMID: 22334863]
  46. Cell. 2023 Jan 5;186(1):17-31 [PMID: 36608652]
  47. Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):13531-13536 [PMID: 29208718]
  48. Phage (New Rochelle). 2020 Sep 1;1(3):137-148 [PMID: 36147828]
  49. Lancet Microbe. 2021 Oct;2(10):e555-e563 [PMID: 35544180]
  50. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0207121 [PMID: 35041506]
  51. Annu Rev Med. 2022 Jan 27;73:197-211 [PMID: 34428079]
  52. Nat Protoc. 2020 Sep;15(9):2867-2890 [PMID: 32709990]
  53. Viruses. 2018 Feb 06;10(2): [PMID: 29415431]
  54. Nat Med. 2019 May;25(5):730-733 [PMID: 31068712]
  55. Lancet Infect Dis. 2022 Aug;22(8):e208-e220 [PMID: 35248167]
  56. BMJ Open. 2022 Dec 9;12(12):e065401 [PMID: 36600337]
  57. Pediatr Res. 2000 Nov;48(5):685-90 [PMID: 11044492]
  58. Toxicon. 2021 Jul 15;197:126-135 [PMID: 33901549]
  59. Clin Microbiol Infect. 2023 Jun;29(6):702-709 [PMID: 36736661]
  60. Curr Opin Virol. 2022 Apr;53:101208 [PMID: 35180534]
  61. J Antibiot (Tokyo). 2023 Aug;76(8):431-473 [PMID: 37291465]
  62. Soc Sci Med. 2022 Apr;298:114818 [PMID: 35247782]
  63. Viruses. 2019 Apr 12;11(4): [PMID: 31013833]

Grants

  1. 218247/Z/19/Z/Wellcome Trust
  2. Confidence in Concept/Medical Research Council
  3. MR/N0137941/1/Medical Research Council

Word Cloud

Created with Highcharts 10.0.0phagesphagetherapyCitizenPhagestrainswithinresistancePhagessamplescitizenLibraryCPLfoundfournamed-patientUKAntimicrobialposesonegreatestthreatsglobalhealthurgentneednewtherapeuticoptionsvirusesinfectkillbacteriaprovidevaluabletooltreatmentmultidrug-resistantinfectionsstudywatercollectedscientistspartprojectwastewaterEnvironmentAgencyyieldedactivityclinicalBPRG1484BPRG1482total169163respectivelydaysreceivingthirdstrainBPRG1486demonstratedcross-reactivity42alreadyheldcollectionSeedlotspreparedcocktailcombiningreducemelanisationinfectionmodelresourcesprotocolsutilisedenabledrapidisolationcharacterisationtargetedmultiplefutureclearlydefinedregulatoryframeworkmadeavailablebasisLibrary:RapidIsolationTreatmentAntibioticResistantInfectionsantimicrobialsciencecocktails

Similar Articles

Cited By