Cited by 817Bacteriophages and microbial interactionsVirus-based gene therapy researchPlant and Fungal Interactions Research

Phage therapy: From biological mechanisms to future directions

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Strathdee, Steffanie A., Hatfull, Graham F., Mutalik, Vivek K., Schooley, Robert T.·2023·Cell

Abstract

Increasing antimicrobial resistance rates have revitalized bacteriophage (phage) research, the natural predators of bacteria discovered over 100 years ago. In order to use phages therapeutically, they should (1) preferably be lytic, (2) kill the bacterial host efficiently, and (3) be fully characterized to exclude side effects. Developing therapeutic phages takes a coordinated effort of multiple stakeholders. Herein, we review the state of the art in phage therapy, covering biological mechanisms, clinical applications, remaining challenges, and future directions involving naturally occurring and genetically modified or synthetic phages.

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Crossref · 10.1016/j.cell.2022.11.017

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  • Phages can eliminate cancer-associated bacteria.

    “Phages can eliminate cancer-associated bacteria, remodel the tumor microenvironment, enhance antitumor immunity, and deliver targeted therapeutic payloads.”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [17]

    In “Other Medical Applications” (page not provided), the paper identifies Helicobacter pylori as a contributor to gastric cancer and reports a prophage active against it. It says this offers hope that phage therapy could target the bacterium’s role in the disease; it does not establish that phages can eliminate cancer-associated bacteria. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Phages enable highly selective removal of cancer-associated bacteria within the gut or tumor niche, avoiding broad collateral damage to commensal communities associated with conventional antibiotics.

    “In parallel, phages enable highly selective removal of cancer-associated bacteria within the gut or tumor niche (Table 1), avoiding the broad collateral damage to commensal communities associated with conventional antibiotics [15,17,20,62,63]”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [17]

    The Phage biology section describes phages’ specific host ranges, and Other Medical Applications discusses selectively targeting gut bacteria and a possible phage target relevant to gastric cancer (page numbers unavailable). But the paper presents the gastric-cancer application as a hope, not established removal of cancer-associated bacteria in the gut or tumor niche. The passages do not establish that such targeting avoids collateral damage to commensal communities compared with conventional antibiotics. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Phages exhibit low inherent toxicity and can be tailored to minimize off-target effects.

    “Phages exhibit low inherent toxicity and can be tailored to minimize off-target effects [15–17,62,99,100]”

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  1. [1]Antimicrobial Resistance Collaborators (2022). Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399, 629– 655. 10.1016/s0140-6736(21)02724-0. 35065702 PMC8841637 · DOI · Paper page
  2. [3]CDC (2022). COVID-19: U.S. Impact on Antimicrobial Resistance, Special Report 2022. 10.15620/cdc:117915. · DOI
  3. [7]O’Neill J (2014). Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Report Government of the United Kingdom. https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf.
  4. [8]Hendrix RW (2002). Bacteriophages: evolution of the majority. Theor Popul Biol 61, 471– 480. 12167366
  5. [9]Nguyen S, Baker K, Padman BS, Patwa R, Dunstan RA, Weston TA, Schlosser K, Bailey B, Lithgow T, Lazarou M, (2017). Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers. mBio 8. 10.1128/mBio.01874-17. PMC5698557 29162715 · DOI
  6. [10]Abedon ST, Thomas-Abedon C, Thomas A, and Mazure H (2011). Bacteriophage prehistory: Is or is not Hankin, 1896, a phage reference? Bacteriophage 1, 174– 178. 10.4161/bact.1.3.16591. 22164351 PMC3225782 · DOI
  7. [12]Summers WC (2012). The strange history of phage therapy. Bacteriophage 2, 130– 133. 10.4161/bact.20757. 23050223 PMC3442826 · DOI
  8. [13]Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, Barr JJ, Reed SL, Rohwer F, Benler S, (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. 10.1128/aac.00954-17. PMC5610518 28807909 · DOI · Paper page
  9. [14]Chan BK, Turner PE, Kim S, Mojibian HR, Elefteriades JA, and Narayan D (2018). Phage treatment of an aortic graft infected with Pseudomonas aeruginosa. Evol Med Public Health 2018, 60– 66. 10.1093/emph/eoy005. 29588855 PMC5842392 · DOI
  10. [15]Dedrick R, Guerrero Bustamante C, Garlena RA, Russell DA, Ford K, Harris K, Gilmour KC, Soothill J, Jacobs-Sera D, Schooley RT, (2019). Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nature Medicine 25, 730– 733. PMC6557439 31068712
  11. [16]Dedrick RM, Smith BE, Cristinziano M, Freeman KG, Jacobs-Sera D, Belessis Y, Whitney Brown A, Cohen KA, Davidson RM, van Duin D, (2022). Phage Therapy of Mycobacterium Infections: Compassionate-use of Phages in Twenty Patients with Drug-Resistant Mycobacterial Disease. Clin Infect Dis. 10.1093/cid/ciac453. PMC9825826 35676823 · DOI · Paper page
  12. [17]Eskenazi A, Lood C, Wubbolts J, Hites M, Balarjishvili N, Leshkasheli L, Askilashvili L, Kvachadze L, van Noort V, Wagemans J, (2022). Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae. Nat Commun 13, 302. 10.1038/s41467-021-27656-z. 35042848 PMC8766457 · DOI
  13. [18]Jennes S, Merabishvili M, Soentjens P, Pang KW, Rose T, Keersebilck E, Soete O, Francois PM, Teodorescu S, Verween G, (2017). Use of bacteriophages in the treatment of colistin-only-sensitive Pseudomonas aeruginosa septicaemia in a patient with acute kidney injury-a case report. Crit Care 21, 129. 10.1186/s13054-017-1709-y. 28583189 PMC5460490 · DOI
  14. [19]Petrovic Fabijan A, Lin RCY, Ho J, Maddocks S, Ben Zakour NL, Iredell JR, and Westmead Bacteriophage Therapy T (2020). Safety of bacteriophage therapy in severe Staphylococcus aureus infection. Nat Microbiol 5, 465– 472. 10.1038/s41564-019-0634-z. 32066959 · DOI
  15. [20]Howard-Varona C, Hargreaves KR, Abedon ST, and Sullivan MB (2017). Lysogeny in nature: mechanisms, impact and ecology of temperate phages. ISME J 11, 1511– 1520. 10.1038/ismej.2017.16. 28291233 PMC5520141 · DOI
  16. [21]Ptashne M (1987). A Genetic Switch (Blackwel Science Ltd and Cell Press).
  17. [22]Wetzel KS, Aull HG, Zack KM, Garlena RA, and Hatfull GF (2020). Protein-Mediated and RNA-Based Origins of Replication of Extrachromosomal Mycobacterial Prophages. mBio 11. 10.1128/mBio.00385-20. PMC7157519 32209683 · DOI
  18. [23]Hendrix RW (1999). Evolution: the long evolutionary reach of viruses. Curr Biol 9, R914– 917. 10607585
  19. [24]Bernheim A, and Sorek R (2020). The pan-immune system of bacteria: antiviral defence as a community resource. Nat Rev Microbiol 18, 113– 119. 10.1038/s41579-019-0278-2. 31695182 · DOI
  20. [25]Leon LM, Park AE, Borges AL, Zhang JY, and Bondy-Denomy J (2021). Mobile element warfare via CRISPR and anti-CRISPR in Pseudomonas aeruginosa. Nucleic Acids Res 49, 2114– 2125. 10.1093/nar/gkab006. 33544853 PMC7913775 · DOI
  21. [27]Pedulla ML, Ford ME, Houtz JM, Karthikeyan T, Wadsworth C, Lewis JA, Jacobs-Sera D, Falbo J, Gross J, Pannunzio NR, (2003). Origins of highly mosaic mycobacteriophage genomes. Cell 113, 171– 182. 12705866
  22. [28]Hendrix RW, Smith MC, Burns RN, Ford ME, and Hatfull GF (1999). Evolutionary relationships among diverse bacteriophages and prophages: all the world’s a phage. Proc Natl Acad Sci U S A 96, 2192– 2197. 10051617 PMC26759
  23. [29]Clokie MR, Millard AD, Letarov AV, and Heaphy S (2011). Phages in nature. Bacteriophage 1, 31– 45. 10.4161/bact.1.1.14942. 21687533 PMC3109452 · DOI
  24. [30]Jordan TC, Burnett SH, Carson S, Caruso SM, Clase K, DeJong RJ, Dennehy JJ, Denver DR, Dunbar D, Elgin SC, (2014). A broadly implementable research course in phage discovery and genomics for first-year undergraduate students. MBio 5, e01051– 01013. 10.1128/mBio.01051-13. 24496795 PMC3950523 · DOI · Paper page
  25. [31]Al-Shayeb B, Sachdeva R, Chen LX, Ward F, Munk P, Devoto A, Castelle CJ, Olm MR, Bouma-Gregson K, Amano Y, (2020). Clades of huge phages from across Earth’s ecosystems. Nature 578, 425– 431. 10.1038/s41586-020-2007-4. 32051592 PMC7162821 · DOI
  26. [32]Borges AL, Lou YC, Sachdeva R, Al-Shayeb B, Penev PI, Jaffe AL, Lei S, Santini JM, and Banfield JF (2022). Widespread stop-codon recoding in bacteriophages may regulate translation of lytic genes. Nat Microbiol 7, 918– 927. 10.1038/s41564-022-01128-6. 35618772 PMC9197471 · DOI
  27. [33]Paez-Espino D, Eloe-Fadrosh EA, Pavlopoulos GA, Thomas AD, Huntemann M, Mikhailova N, Rubin E, Ivanova NN, and Kyrpides NC (2016). Uncovering Earth’s virome. Nature 536, 425– 430. 10.1038/nature19094. 27533034 · DOI
  28. [34]Nayfach S, Páez-Espino D, Call L, Low SJ, Sberro H, Ivanova NN, Proal AD, Fischbach MA, Bhatt AS, Hugenholtz P, and Kyrpides NC (2021). Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome. Nature Microbiology 6, 960– 970. 10.1038/s41564-021-00928-6. PMC8241571 34168315 · DOI · Paper page
  29. [35]Chan BK, Sistrom M, Wertz JE, Kortright KE, Narayan D, and Turner PE (2016). Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa. Sci Rep 6, 26717. 10.1038/srep26717. 27225966 PMC4880932 · DOI
  30. [36]Kortright KE, Chan BK, Evans BR, and Turner PE (2022). Arms race and fluctuating selection dynamics in Pseudomonas aeruginosa bacteria coevolving with phage OMKO1. J Evol Biol. 10.1111/jeb.14095. 36168737 · DOI
  31. [37]Philipson CW, Voegtly LJ, Lueder MR, Long KA, Rice GK, Frey KG, Biswas B, Cer RZ, Hamilton T, and Bishop-Lilly KA (2018). Characterizing Phage Genomes for Therapeutic Applications. Viruses 10. 10.3390/v10040188. PMC5923482 29642590 · DOI
  32. [38]Dedrick RM, Smith BE, Garlena RA, Russell DA, Aull HG, Mahalingam V, Divens AM, Guerrero-Bustamante CA, Zack KM, Abad L, (2021). Mycobacterium abscessus Strain Morphotype Determines Phage Susceptibility, the Repertoire of Therapeutically Useful Phages, and Phage Resistance. mBio 12. 10.1128/mBio.03431-20. PMC8092298 33785625 · DOI
  33. [40]Mutalik VK, Adler BA, Rishi HS, Piya D, Zhong C, Koskella B, Kutter EM, Calendar R, Novichkov PS, Price MN, (2020). High-throughput mapping of the phage resistance landscape in E. coli. PLoS Biol 18, e3000877. 10.1371/journal.pbio.3000877. 33048924 PMC7553319 · DOI · Paper page
  34. [41]Adler BA, Kazakov AE, Zhong C, Liu H, Kutter E, Lui LM, Nielsen TN, Carion H, Deutschbauer AM, Mutalik VK, and Arkin AP (2021). The genetic basis of phage susceptibility, cross-resistance and host-range in Salmonella. Microbiology (Reading) 167. 10.1099/mic.0.001126. PMC8744999 34910616 · DOI · Paper page
  35. [42]Kortright KE, Chan BK, and Turner PE (2020). High-throughput discovery of phage receptors using transposon insertion sequencing of bacteria. Proc Natl Acad Sci U S A 117, 18670– 18679. 10.1073/pnas.2001888117. 32675236 PMC7414163 · DOI
  36. [43]Maffei E, Shaidullina A, Burkolter M, Heyer Y, Estermann F, Druelle V, Sauer P, Willi L, Michaelis S, Hilbi H, (2021). Systematic exploration of Escherichia coli phage-host interactions with the BASEL phage collection. PLoS Biol 19, e3001424. 10.1371/journal.pbio.3001424. 34784345 PMC8594841 · DOI
  37. [44]Wright RCT, Friman VP, Smith MCM, and Brockhurst MA (2019). Resistance Evolution against Phage Combinations Depends on the Timing and Order of Exposure. mBio 10. 10.1128/mBio.01652-19. PMC6759759 31551330 · DOI
  38. [45]Tanji Y, Shimada T, Yoichi M, Miyanaga K, Hori K, and Unno H (2004). Toward rational control of Escherichia coli O157:H7 by a phage cocktail. Appl Microbiol Biotechnol 64, 270– 274. 10.1007/s00253-003-1438-9. 13680205 · DOI
  39. [46]Kortright KE, Chan BK, Koff JL, and Turner PE (2019). Phage Therapy: A Renewed Approach to Combat Antibiotic-Resistant Bacteria. Cell Host Microbe 25, 219– 232. 10.1016/j.chom.2019.01.014. 30763536 · DOI
  40. [47]Gordillo Altamirano FL, and Barr JJ (2021). Unlocking the next generation of phage therapy: the key is in the receptors. Curr Opin Biotechnol 68, 115– 123. 10.1016/j.copbio.2020.10.002. 33202354 · DOI
  41. [48]Gurney J, Brown SP, Kaltz O, and Hochberg ME (2020). Steering Phages to Combat Bacterial Pathogens. Trends Microbiol 28, 85– 94. 10.1016/j.tim.2019.10.007. 31744662 PMC6980653 · DOI
  42. [49]Mangalea MR, and Duerkop BA (2020). Fitness Trade-Offs Resulting from Bacteriophage Resistance Potentiate Synergistic Antibacterial Strategies. Infect Immun 88. 10.1128/IAI.00926-19. PMC7309606 32094257 · DOI
  43. [50]Torres-Barcelo C, Turner PE, and Buckling A (2022). Mitigation of evolved bacterial resistance to phage therapy. Curr Opin Virol 53, 101201. 10.1016/j.coviro.2022.101201. 35180532 · DOI
  44. [51]Glonti T, and Pirnay JP (2022). In Vitro Techniques and Measurements of Phage Characteristics That Are Important for Phage Therapy Success. Viruses 14. 10.3390/v14071490. PMC9323186 35891470 · DOI
  45. [52]Goller PC, Elsener T, Lorge D, Radulovic N, Bernardi V, Naumann A, Amri N, Khatchatourova E, Coutinho FH, Loessner MJ, and Gomez-Sanz E (2021). Multi-species host range of staphylococcal phages isolated from wastewater. Nat Commun 12, 6965. 10.1038/s41467-021-27037-6. 34845206 PMC8629997 · DOI
  46. [53]Suh GA, Lodise TP, Tamma PD, Knisely JM, Alexander J, Aslam S, Barton KD, Bizzell E, Totten KMC, Campbell JL, (2022). Considerations for the Use of Phage Therapy in Clinical Practice. Antimicrob Agents Chemother 66, e0207121. 10.1128/AAC.02071-21. 35041506 PMC8923208 · DOI
  47. [54]Aslam S, Lampley E, Wooten D, Karris M, Benson C, Strathdee S, and Schooley RT (2020). Lessons Learned From the First 10 Consecutive Cases of Intravenous Bacteriophage Therapy to Treat Multidrug-Resistant Bacterial Infections at a Single Center in the United States. Open Forum Infect Dis 7, ofaa389. 10.1093/ofid/ofaa389. 33005701 PMC7519779 · DOI
  48. [56]Verbeken G, and Pirnay JP (2022). European regulatory aspects of phage therapy: magistral phage preparations. Curr Opin Virol 52, 24– 29. 10.1016/j.coviro.2021.11.005. 34801778 · DOI
  49. [57]Onsea J, Uyttebroek S, Chen B, Wagemans J, Lood C, Van Gerven L, Spriet I, Devolder D, Debaveye Y, Depypere M, (2021). Bacteriophage Therapy for Difficult-to-Treat Infections: The Implementation of a Multidisciplinary Phage Task Force (The PHAGEFORCE Study Protocol). Viruses 13. 10.3390/v13081543. PMC8402896 34452408 · DOI
  50. [58]Iredell J, and Khatami A (2022). Standardised Treatment And Monitoring Protocol to assess safety and tolerability of phage therapy in adults and children (STAMP study). https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382817&isReview=true. PMC9743374 36600337
  51. [59]Żaczek M, Górski A, Weber-Dąbrowska B, Letkiewicz S, Fortuna W, Rogóż P, Pasternak E, and Międzybrodzki R (2022). A Thorough Synthesis of Phage Therapy Unit Activity in Poland-Its History, Milestones and International Recognition. Viruses 14. 10.3390/v14061170. PMC9227841 35746642 · DOI
  52. [60]Suh GA, Lodise TP, Tamma PD, Knisely JM, Alexander J, Aslam S, Barton KD, Bizzell E, Totten KMC, Campbell JL, (2022). Considerations for the Use of Phage Therapy in Clinical Practice. Antimicrob Agents Chemother 66, e0207121. 10.1128/aac.02071-21. 35041506 PMC8923208 · DOI
  53. [62]Liu D, Van Belleghem JD, de Vries CR, Burgener E, Chen Q, Manasherob R, Aronson JR, Amanatullah DF, Tamma PD, and Suh GA (2021). The Safety and Toxicity of Phage Therapy: A Review of Animal and Clinical Studies. Viruses 13. 10.3390/v13071268. PMC8310247 34209836 · DOI
  54. [63]Jerne NK, and Avegno P (1956). The development of the phage-inactivating properties of serum during the course of specific immunization of an animal: reversible and irreversible inactivation. J Immunol 76, 200– 208. 13306955
  55. [64]Dan JM, Lehman SM, Al-kolla R, Penziner S, Afshar K, Yung G, Golts E, Law N, Logan C, Kovach Z, (2022). Development of Host Immune Response to Bacteriophage in a Lung Transplant Recipient on Adjunctive Phage Therapy for a Multidrug-Resistant Pneumonia. The Journal of Infectious Diseases. 10.1093/infdis/jiac368. PMC10152496 36082999 · DOI
  56. [65]Dedrick RM, Freeman KG, Nguyen JA, Bahadirli-Talbott A, Smith BE, Wu AE, Ong AS, Lin CT, Ruppel LC, Parrish NM, (2021). Potent antibody-mediated neutralization limits bacteriophage treatment of a pulmonary Mycobacterium abscessus infection. Nat Med 27, 1357– 1361. 10.1038/s41591-021-01403-9. 34239133 PMC8571776 · DOI
  57. [66]Chan SK, Zhao Z, Penziner S, Khong E, Pride D, Schooley RT, and Steinmetz NF (2022). Isolation of a Peptide That Binds to Pseudomonas aeruginosa Lytic Bacteriophage. ACS Omega 7, 38053– 38060. 10.1021/acsomega.2c05539. 36312416 PMC9609082 · DOI
  58. [67]Schooley RT, and Strathdee S (2020). Treat phage like living antibiotics. Nature Microbiology 5, 391– 392. 10.1038/s41564-019-0666-4. 32103171 · DOI
  59. [68]Jault P, Leclerc T, Jennes S, Pirnay JP, Que YA, Resch G, Rousseau AF, Ravat F, Carsin H, Le Floch R, (2019). Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial. Lancet Infect Dis 19, 35– 45. 10.1016/s1473-3099(18)30482-1. 30292481 · DOI
  60. [69]Sarker SA, Sultana S, Reuteler G, Moine D, Descombes P, Charton F, Bourdin G, McCallin S, Ngom-Bru C, Neville T, (2016). Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh. EBioMedicine 4, 124– 137. 10.1016/j.ebiom.2015.12.023. 26981577 PMC4776075 · DOI
  61. [70]U.S. National Library of Medicine (2022). ClinicalTrials.gov. 28792816
  62. [71]Harper DR, Parracho H, Walker J, Sharp R, Hughes G, Werthén M, Lehman S, and Morales S (2014). Bacteriophages and Biofilms. Antibiotics (Basel) 3, 270– 284. 10.3390/antibiotics3030270. · DOI
  63. [72]Dabrowska K (2019). Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review. Med Res Rev 39, 2000– 2025. 10.1002/med.21572. 30887551 PMC6767042 · DOI
  64. [73]Dabrowska K, and Abedon ST (2019). Pharmacologically Aware Phage Therapy: Pharmacodynamic and Pharmacokinetic Obstacles to Phage Antibacterial Action in Animal and Human Bodies. Microbiol Mol Biol Rev 83. 10.1128/MMBR.00012-19. PMC6822990 31666296 · DOI
  65. [74]Henry M, Biswas B, Vincent L, Mokashi V, Schuch R, Bishop-Lilly KA, and Sozhamannan S (2012). Development of a high throughput assay for indirectly measuring phage growth using the OmniLog(TM) system. Bacteriophage 2, 159– 167. 10.4161/bact.21440. 23275867 PMC3530525 · DOI
  66. [75]Mutalik VK, and Arkin AP (2022). A Phage Foundry Framework to Systematically Develop Viral Countermeasures to Combat Antibiotic-Resistant Bacterial Pathogens. iScience 25, 104121. 10.1016/j.isci.2022.104121. 35402883 PMC8983348 · DOI · Paper page
  67. [76]Segall AM, Roach DR, and Strathdee SA (2019). Stronger together? Perspectives on phage-antibiotic synergy in clinical applications of phage therapy. Curr Opin Microbiol 51, 46– 50. 10.1016/j.mib.2019.03.005. 31226502 · DOI
  68. [77]Pires DP, Cleto S, Sillankorva S, Azeredo J, and Lu TK (2016). Genetically Engineered Phages: a Review of Advances over the Last Decade. Microbiol Mol Biol Rev 80, 523– 543. 10.1128/mmbr.00069-15. 27250768 PMC4981678 · DOI
  69. [78]Hohn B, and Murray K (1977). Packaging recombinant DNA molecules into bacteriophage particles in vitro. Proc Natl Acad Sci U S A 74, 3259– 3263. 10.1073/pnas.74.8.3259. 333431 PMC431522 · DOI
  70. [79]Thomas M, Cameron JR, and Davis RW (1974). Viable Molecular Hybrids of Bacteriophage Lambda and Eukaryotic DNA. Proceedings of the National Academy of Sciences 71, 4579– 4583. doi: 10.1073/pnas.71.11.4579. PMC433931 4216019 · DOI
  71. [80]Nick JA, Dedrick RM, Gray AL, Vladar EK, Smith BE, Freeman KG, Malcolm KC, Epperson LE, Hasan NA, Hendrix J, (2022). Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection. Cell. 10.1016/j.cell.2022.04.024. PMC9840467 35568033 · DOI · Paper page
  72. [81]Court DL, Sawitzke JA, and Thomason LC (2002). Genetic engineering using homologous recombination. Annu Rev Genet 36, 361– 388. 12429697
  73. [82]Marinelli LJ, Piuri M, Swigonova Z, Balachandran A, Oldfield LM, van Kessel JC, and Hatfull GF (2008). BRED: a simple and powerful tool for constructing mutant and recombinant bacteriophage genomes. PLoS ONE 3, e3957. 10.1371/journal.pone.0003957. 19088849 PMC2597740 · DOI
  74. [83]Grigonyte AM, Harrison C, MacDonald PR, Montero-Blay A, Tridgett M, Duncan J, Sagona AP, Constantinidou C, Jaramillo A, and Millard A (2020). Comparison of CRISPR and Marker-Based Methods for the Engineering of Phage T7. Viruses 12. 10.3390/v12020193. PMC7077284 32050613 · DOI
  75. [84]Sarkis GJ, Jacobs WR Jr., and Hatfull GF (1995). L5 luciferase reporter mycobacteriophages: a sensitive tool for the detection and assay of live mycobacteria. Mol Microbiol 15, 1055– 1067. 7623662
  76. [85]Hatoum-Aslan A (2018). Phage Genetic Engineering Using CRISPR−Cas Systems. Viruses 10. 10.3390/v10060335. PMC6024849 29921752 · DOI
  77. [86]Łobocka M, Dąbrowska K, and Górski A (2021). Engineered Bacteriophage Therapeutics: Rationale, Challenges and Future. BioDrugs 35, 255– 280. 10.1007/s40259-021-00480-z. 33881767 PMC8084836 · DOI
  78. [87]Wetzel KS, Guerrero-Bustamante CA, Dedrick RM, Ko CC, Freeman KG, Aull HG, Divens AM, Rock JM, Zack KM, and Hatfull GF (2021). CRISPY-BRED and CRISPY-BRIP: efficient bacteriophage engineering. Sci Rep 11, 6796. 10.1038/s41598-021-86112-6. 33762639 PMC7990910 · DOI
  79. [88]Guan J, Oromí-Bosch A, Mendoza SD, Karambelkar S, Berry JD, and Bondy-Denomy J (2022). Bacteriophage genome engineering with CRISPR–Cas13a. Nature Microbiology. 10.1038/s41564-022-01243-4. PMC9722621 36316452 · DOI
  80. [89]Adler BA, Hessler T, Cress BF, Lahiri A, Mutalik VK, Barrangou R, Banfield J, and Doudna JA (2022). Broad-spectrum CRISPR-Cas13a enables efficient phage genome editing. Nature Microbiology. 10.1038/s41564-022-01258-x. PMC9712115 36316451 · DOI
  81. [90]Guan J, and Bondy-Denomy J (2020). Intracellular Organization by Jumbo Bacteriophages. Journal of Bacteriology 203, e00362– 00320. doi: 10.1128/JB.00362-20. 32868402 PMC7950403 · DOI
  82. [91]Pirnay JP (2020). Phage Therapy in the Year 2035. Front Microbiol 11, 1171. 10.3389/fmicb.2020.01171. 32582107 PMC7284012 · DOI
  83. [92]Yukgehnaish K, Rajandas H, Parimannan S, Manickam R, Marimuthu K, Petersen B, Clokie MRJ, Millard A, and Sicheritz-Ponten T (2022). PhageLeads: Rapid Assessment of Phage Therapeutic Suitability Using an Ensemble Machine Learning Approach. Viruses 14. 10.3390/v14020342. PMC8879740 35215934 · DOI
  84. [93]Anzalone AV, Koblan LW, and Liu DR (2020). Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nature Biotechnology 38, 824– 844. 10.1038/s41587-020-0561-9. 32572269 · DOI · Paper page
  85. [94]Rubin BE, Diamond S, Cress BF, Crits-Christoph A, Lou YC, Borges AL, Shivram H, He C, Xu M, Zhou Z, (2022). Species- and site-specific genome editing in complex bacterial communities. Nature Microbiology 7, 34– 47. 10.1038/s41564-021-01014-7. PMC9261505 34873292 · DOI
  86. [95]Pryor JM, Potapov V, Bilotti K, Pokhrel N, and Lohman GJS (2022). Rapid 40 kb Genome Construction from 52 Parts through Data-optimized Assembly Design. ACS Synthetic Biology 11, 2036– 2042. 10.1021/acssynbio.1c00525. 35613368 PMC9208013 · DOI
  87. [96]Silverman AD, Karim AS, and Jewett MC (2020). Cell-free gene expression: an expanded repertoire of applications. Nature Reviews Genetics 21, 151– 170. 10.1038/s41576-019-0186-3. 31780816 · DOI
  88. [97]Garenne D, Bowden S, and Noireaux V (2021). Cell-free expression and synthesis of viruses and bacteriophages: applications to medicine and nanotechnology. Current Opinion in Systems Biology 28, 100373. 10.1016/j.coisb.2021.100373. · DOI
  89. [98]Kilcher S, Studer P, Muessner C, Klumpp J, and Loessner MJ (2018). Cross-genus rebooting of custom-made, synthetic bacteriophage genomes in L-form bacteria. Proceedings of the National Academy of Sciences 115, 567– 572. doi: 10.1073/pnas.1714658115. PMC5776983 29298913 · DOI
  90. [99]Kilcher S, and Loessner MJ (2019). Engineering Bacteriophages as Versatile Biologics. Trends Microbiol 27, 355– 367. 10.1016/j.tim.2018.09.006. 30322741 · DOI
  91. [100]Emslander Q, Vogele K, Braun P, Stender J, Willy C, Joppich M, Hammerl JA, Abele M, Meng C, Pichlmair A, (2022). Cell-free production of personalized therapeutic phages targeting multidrug-resistant bacteria. Cell Chem Biol. 10.1016/j.chembiol.2022.06.003. 35820417 · DOI
  92. [102]Kolodziejczyk AA, Zheng D, Shibolet O, and Elinav E (2019). The role of the microbiome in NAFLD and NASH. EMBO Molecular Medicine 11, e9302. 10.15252/emmm.201809302. 30591521 PMC6365925 · DOI · Paper page
  93. [103]Duan Y, Llorente C, Lang S, Brandl K, Chu H, Jiang L, White RC, Clarke TH, Nguyen K, Torralba M, (2019). Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature 575, 505– 511. 10.1038/s41586-019-1742-x. 31723265 PMC6872939 · DOI
  94. [105]Hsu CL, Duan Y, Fouts DE, and Schnabl B (2021). Intestinal virome and therapeutic potential of bacteriophages in liver disease. J Hepatol 75, 1465– 1475. 10.1016/j.jhep.2021.08.003. 34437908 PMC8929164 · DOI
  95. [106]Galtier M, De Sordi L, Sivignon A, de Vallée A, Maura D, Neut C, Rahmouni O, Wannerberger K, Darfeuille-Michaud A, Desreumaux P, (2017). Bacteriophages Targeting Adherent Invasive Escherichia coli Strains as a Promising New Treatment for Crohn’s Disease. J Crohns Colitis 11, 840– 847. 10.1093/ecco-jcc/jjw224. 28130329 · DOI
  96. [108]Ferreira R, Sousa C, Goncalves RFS, Pinheiro AC, Oleastro M, Wagemans J, Lavigne R, Figueiredo C, Azeredo J, and Melo LDR (2022). Characterization and Genomic Analysis of a New Phage Infecting Helicobacter pylori. Int J Mol Sci 23. 10.3390/ijms23147885. PMC9319048 35887231 · DOI
  97. [109]Bhandare S, Colom J, Baig A, Ritchie JM, Bukhari H, Shah MA, Sarkar BL, Su J, Wren B, Barrow P, and Atterbury RJ (2019). Reviving Phage Therapy for the Treatment of Cholera. J Infect Dis 219, 786– 794. 10.1093/infdis/jiy563. 30395214 PMC7610978 · DOI
  98. [110]Hatfull GF (2014). Mycobacteriophages: windows into tuberculosis. PLoS Pathog 10, e1003953. 10.1371/journal.ppat.1003953. 24651299 PMC3961340 · DOI
  99. [111]Jackson K, Peivandi A, Fogal M, Tian L, and Hosseinidoust Z (2021). Filamentous Phages as Building Blocks for Bioactive Hydrogels. ACS Appl Bio Mater 4, 2262– 2273. 10.1021/acsabm.0c01557. 35014350 · DOI
  100. [112]Sutcliffe SG, Shamash M, Hynes AP, and Maurice CF (2021). Common Oral Medications Lead to Prophage Induction in Bacterial Isolates from the Human Gut. Viruses 13. 10.3390/v13030455. PMC8000485 33799646 · DOI
  101. [113]Hu J, Ye H, Wang S, Wang J, and Han D (2021). Prophage Activation in the Intestine: Insights Into Functions and Possible Applications. Front Microbiol 12, 785634. 10.3389/fmicb.2021.785634. 34966370 PMC8710666 · DOI
  102. [114]Boling L, Cuevas DA, Grasis JA, Kang HS, Knowles B, Levi K, Maughan H, McNair K, Rojas MI, Sanchez SE, (2020). Dietary prophage inducers and antimicrobials: toward landscaping the human gut microbiome. Gut Microbes 11, 721– 734. 10.1080/19490976.2019.1701353. 31931655 PMC7524278 · DOI
  103. [115]Baaziz H, Baker ZR, Franklin HC, and Hsu BB (2022). Rehabilitation of a misbehaving microbiome: phages for the remodeling of bacterial composition and function. iScience 25, 104146. 10.1016/j.isci.2022.104146. 35402871 PMC8991392 · DOI
  104. [116]Jacobs WR Jr., Barletta RG, Udani R, Chan J, Kalkut G, Sosne G, Kieser T, Sarkis GJ, Hatfull GF, and Bloom BR (1993). Rapid assessment of drug susceptibilities of Mycobacterium tuberculosis by means of luciferase reporter phages. Science 260, 819– 822. 8484123
  105. [117]Shan J, Jia Y, Teulières L, Patel F, and Clokie MRJ (2021). Targeting Multicopy Prophage Genes for the Increased Detection of Borrelia burgdorferi Sensu Lato (s.l.), the Causative Agents of Lyme Disease, in Blood. Front Microbiol 12, 651217. 10.3389/fmicb.2021.651217. 33790883 PMC8005754 · DOI
  106. [118]Sozhamannan S, and Hofmann ER (2020). The State of the Art in Biodefense Related Bacterial Pathogen Detection Using Bacteriophages: How It Started and How It’s Going. Viruses 12. 10.3390/v12121393. PMC7762055 33291831 · DOI
  107. [119]Loponte R, Pagnini U, Iovane G, and Pisanelli G (2021). Phage Therapy in Veterinary Medicine. Antibiotics 10, 421. 33920369 PMC8069180
  108. [120]Huang Y, Wang W, Zhang Z, Gu Y, Huang A, Wang J, and Hao H (2022). Phage Products for Fighting Antimicrobial Resistance. Microorganisms 10, 1324. 35889048 PMC9324367
  109. [121]Sklar IB, and Joerger RD (2001). Attempts to utilize bacteriophage to combat Salmonella enterica serovar entemtidis infection in chickens. Journal of Food Safety 21, 15– 29. 10.1111/j.1745-4565.2001.tb00305.x. · DOI
  110. [122]Atterbury RJ, Van Bergen MA, Ortiz F, Lovell MA, Harris JA, De Boer A, Wagenaar JA, Allen VM, and Barrow PA (2007). Bacteriophage therapy to reduce salmonella colonization of broiler chickens. Appl Environ Microbiol 73, 4543– 4549. 10.1128/aem.00049-07. 17526794 PMC1932804 · DOI
  111. [123]Ahmadi M, Karimi Torshizi MA, Rahimi S, and Dennehy JJ (2016). Prophylactic Bacteriophage Administration More Effective than Post-infection Administration in Reducing Salmonella enterica serovar Enteritidis Shedding in Quail. Front Microbiol 7, 1253. 10.3389/fmicb.2016.01253. 27555842 PMC4977285 · DOI
  112. [124]Nale JY, Vinner GK, Lopez VC, Thanki AM, Phothaworn P, Thiennimitr P, Garcia A, AbuOun M, Anjum MF, Korbsrisate S, (2020). An Optimized Bacteriophage Cocktail Can Effectively Control Salmonella in vitro and in Galleria mellonella. Front Microbiol 11, 609955. 10.3389/fmicb.2020.609955. 33552020 PMC7858669 · DOI
  113. [125]El-Gohary FA, Huff WE, Huff GR, Rath NC, Zhou ZY, and Donoghue AM (2014). Environmental augmentation with bacteriophage prevents colibacillosis in broiler chickens. Poult Sci 93, 2788– 2792. 10.3382/ps.2014-04282. 25214555 · DOI
  114. [126]O’Flaherty S, Ross RP, Flynn J, Meaney WJ, Fitzgerald GF, and Coffey A (2005). Isolation and characterization of two anti-staphylococcal bacteriophages specific for pathogenic Staphylococcus aureus associated with bovine infections. Lett Appl Microbiol 41, 482– 486. 10.1111/j.1472-765X.2005.01781.x. 16305674 · DOI
  115. [127]Thanki AM, Mignard G, Atterbury RJ, Barrow P, Millard AD, and Clokie MRJ (2022). Prophylactic Delivery of a Bacteriophage Cocktail in Feed Significantly Reduces Salmonella Colonization in Pigs. Microbiol Spectr 10, e0042222. 10.1128/spectrum.00422-22. 35579475 PMC9241700 · DOI
  116. [128]Gendre J, Ansaldi M, Olivenza DR, Denis Y, Casadesús J, and Ginet N (2022). Genetic Mining of Newly Isolated Salmophages for Phage Therapy. Int J Mol Sci 23. 10.3390/ijms23168917. PMC9409062 36012174 · DOI
  117. [129]Damborg P, Broens EM, Chomel BB, Guenther S, Pasmans F, Wagenaar JA, Weese JS, Wieler LH, Windahl U, Vanrompay D, and Guardabassi L (2016). Bacterial Zoonoses Transmitted by Household Pets: State-of-the-Art and Future Perspectives for Targeted Research and Policy Actions. J Comp Pathol 155, S27– 40. 10.1016/j.jcpa.2015.03.004. 25958184 · DOI
  118. [130]Squires RA (2018). Bacteriophage therapy for management of bacterial infections in veterinary practice: what was once old is new again. N Z Vet J 66, 229– 235. 10.1080/00480169.2018.1491348. 29925297 · DOI
  119. [131]Hawkins C, Harper D, Burch D, Anggård E, and Soothill J (2010). Topical treatment of Pseudomonas aeruginosa otitis of dogs with a bacteriophage mixture: a before/after clinical trial. Vet Microbiol 146, 309– 313. 10.1016/j.vetmic.2010.05.014. 20627620 · DOI
  120. [132]Silva EC, Oliveira TJ, Moreli FC, Harada LK, Vila M, and Balcão VM (2021). Newly isolated lytic bacteriophages for Staphylococcus intermedius, structurally and functionally stabilized in a hydroxyethylcellulose gel containing choline geranate: Potential for transdermal permeation in veterinary phage therapy. Res Vet Sci 135, 42– 58. 10.1016/j.rvsc.2020.12.013. 33440244 · DOI
  121. [133]Austin BA, D. A (2012). Bacterial Fish Pathogens, 5 Edition (Springer Dordrecht). 10.1007/978-94-007-4884-2. · DOI
  122. [134]Svircev A, Roach D, and Castle A (2018). Framing the Future with Bacteriophages in Agriculture. Viruses 10, 218. 29693561 PMC5977211
  123. [135]Richards GP (2014). Bacteriophage remediation of bacterial pathogens in aquaculture: a review of the technology. Bacteriophage 4, e975540. 10.4161/21597081.2014.975540. 26713223 PMC4590005 · DOI
  124. [136]Park SC, and Nakai T (2003). Bacteriophage control of Pseudomonas plecoglossicida infection in ayu Plecoglossus altivelis. Dis Aquat Organ 53, 33– 39. 10.3354/dao053033. 12608566 · DOI
  125. [137]Meaden S, and Koskella B (2013). Exploring the risks of phage application in the environment. Front Microbiol 4, 358. 10.3389/fmicb.2013.00358. 24348468 PMC3843224 · DOI
  126. [138]Buttimer C, McAuliffe O, Ross RP, Hill C, O’Mahony J, and Coffey A (2017). Bacteriophages and Bacterial Plant Diseases. Front Microbiol 8, 34. 10.3389/fmicb.2017.00034. 28163700 PMC5247434 · DOI
  127. [140]Das M, Bhowmick TS, Ahern SJ, Young R, and Gonzalez CF (2015). Control of Pierce’s Disease by Phage. PLoS One 10, e0128902. 10.1371/journal.pone.0128902. 26107261 PMC4479439 · DOI
  128. [141]Boyetchko S, and Svircev A (2013). A novel approach for developing microbial biopesticides (CABI International). 10.1079/9781780642574.0037. · DOI
  129. [142]Alomari MMM, Dec M, and Urban-Chmiel R (2021). Bacteriophages as an Alternative Method for Control of Zoonotic and Foodborne Pathogens. Viruses 13. 10.3390/v13122348. PMC8709489 34960617 · DOI
  130. [143]Sørensen MCH, Gencay YE, Fanger F, Chichkova MAT, Mazúrová M, Klumpp J, Nielsen EM, and Brøndsted L (2021). Identification of Novel Phage Resistance Mechanisms in Campylobacter jejuni by Comparative Genomics. Front Microbiol 12, 780559. 10.3389/fmicb.2021.780559. 34970240 PMC8713573 · DOI
  131. [144]Jończyk-Matysiak E, Owczarek B, Popiela E, Świtała-Jeleń K, Migdał P, Cieślik M, Łodej N, Kula D, Neuberg J, Hodyra-Stefaniak K, (2021). Isolation and Characterization of Phages Active against Paenibacillus larvae Causing American Foulbrood in Honeybees in Poland. Viruses 13. 10.3390/v13071217. PMC8310151 34201873 · DOI
  132. [145]Jończyk-Matysiak E, Popiela E, Owczarek B, Hodyra-Stefaniak K, Świtała-Jeleń K, Łodej N, Kula D, Neuberg J, Migdał P, Bagińska N, (2020). Phages in Therapy and Prophylaxis of American Foulbrood - Recent Implications From Practical Applications. Front Microbiol 11, 1913. 10.3389/fmicb.2020.01913. 32849478 PMC7432437 · DOI
  133. [146]Runa V, Wenk J, Bengtsson S, Jones BV, and Lanham AB (2021). Bacteriophages in Biological Wastewater Treatment Systems: Occurrence, Characterization, and Function. Front Microbiol 12, 730071. 10.3389/fmicb.2021.730071. 34803947 PMC8600467 · DOI
  134. [147]Jacquemot L, Bettarel Y, Monjol J, Corre E, Halary S, Desnues C, Bouvier T, Ferrier-Pagès C, and Baudoux AC (2018). Therapeutic Potential of a New Jumbo Phage That Infects Vibrio coralliilyticus, a Widespread Coral Pathogen. Front Microbiol 9, 2501. 10.3389/fmicb.2018.02501. 30405564 PMC6207643 · DOI

Cited by

Sorted by citations

Authors
Strathdee, S. A., Hatfull, G. F., Mutalik, V. K., & Schooley, R. T.
Affiliations
  • University of California San Diego (US)
  • University of Pittsburgh (US)
  • Lawrence Berkeley National Laboratory (US)
Corresponding author
Strathdee, Steffanie A.
Venue
Cell
Publisher
Elsevier BV
Published
2023-01
Volume
186
Issue
1
Pages
17-31
ISSN
0092-8674 (ISSN-L)
OpenAlex
W4313560729
Cited by
817
References
3
Citations by year
2026: 238 · 2025: 290 · 2024: 203 · 2023: 86
FWCI
24.32
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • U.S. Department of Energy (-AC02-05CH11231, 05CH11231, DE AC02 05CH11231, DE-AC02-)
  • University of California, San Diego
  • National Institute of General Medical Sciences (DE-AC02-05CH11231, R35GM131729)
  • National Institute of Allergy and Infectious Diseases (UM1AI104681)
  • National Institute of Environmental Health Sciences (R01ES011184)
  • Lawrence Berkeley National Laboratory (AC02‐05CH11231, DE-AC02-05CH11231, 05CH11231)
Topics
  • Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Plant and Fungal Interactions Research
Keywords
phage therapy, bacteriophages, antimicrobial resistance, lytic phages, phage-host interactions, phage characterization
MeSH terms
Phage Therapy, Bacteria, Bacteriophages

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