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General characteristics, results and prospects for the clinical application of bacteriophage therapy

https://doi.org/10.21518/ms2023-106

Abstract

Viruses are the most numerous biological creatures in the biosphere of the globe. Their number is huge ~ 1031, and bacteriophages are the most numerous group of environmental viruses. It is not surprising that in such an environment and in the human body and on its skin, a large community of various viruses has formed, representing a viral metagenome (virome). This virome includes not only viruses that penetrate into the cells of the human body and replicate in them using cell material, but also viruses that target only bacteria, namely bacteriophages. The ability of lytic bacteriophages with high specificity to kill certain bacteria was discovered in the 1920s. XX century. In this regard, lytic bacteriophages have been proposed and successfully used for the treatment of acute intestinal infections. However, the advent of antibiotics, the use of which was initially more effective for the treatment of bacterial infections, has led to the abandonment of phage therapy in Western countries. The return of attention of scientists and practical healthcare professionals to the use of bacteriophages as drugs occurred due to the formation and spread of multidrug resistance of pathogenic bacteria to the most commonly used antibacterial drugs. The incidence of various bacterial infections is not decreasing. This review provides information on a number of successful clinical and experimental applications of bacteriophage preparations in various diseases that are caused by bacteria, or bacterial inflammation has arisen as a complication of the underlying disease. It is very important that bacteriophages have a synergistic effect with antibacterial drugs. Bacteriophage therapy is considered as a potentially effective method of treatment.

About the Authors

P. V. Nacharov
Saint Petersburg Research Institute of Ear, Throat, Nose and Speech
Russian Federation

Petr V. Nacharov, Cand. Sci. (Med.), Associate Professor, Head of the Research Department of Laboratory and Diagnostic

9, Bronnitskaya St., St Petersburg, 190013, Russia 



A. A. Krivopalov
Saint Petersburg Research Institute of Ear, Throat, Nose and Speech
Russian Federation

Aleksandr A. Krivopalov, Dr. Sci. (Med.), Associate Professor, Head of the Research Department of Upper Respiratory Pathology 

9, Bronnitskaya St., St Petersburg, 190013, Russia 



T. I. Shustova
Saint Petersburg Research Institute of Ear, Throat, Nose and Speech
Russian Federation

Tatiana I. Shustova, Dr. Sci. (Biol.), Professor, Chief Researcher 

9, Bronnitskaya St., St Petersburg, 190013, Russia 



References

1. Breitbart M., Rohwer F. Here a virus, there a virus, everywhere the same virus? Trends Microbiol. 2005;13(6):278–284. https://doi.org/10.1016/j.tim.2005.04.003.

2. Rohwer F. Global phage diversity. Cell. 2003;113(2):141. https://doi.org/10.1016/s0092-8674(03)00276-9.

3. Golovin C. Bacteriophages: killers as saviors. Nauka i Zhizn. 2017;(6):26–33. (In Russ.) Available at: https://nkj.ru/archive/articles/31498/.

4. Wiertsema S.P., van Bergenhenegouwen J., Garssen J., Knippels L.M.J. The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients. 2021;13(3):886. https://doi.org/10.3390/nu13030886.

5. Gregory A.C., Zablocki O., Zayed A.A., Howell A., Bolduc B., Sullivan M.B. The Gut Virome Database Reveals Age-Dependent Patterns of Virome Diversity in the Human Gut. Cell Host Microbe. 2020;28(5):724–740.e8. https://doi.org/10.1016/j.chom.2020.08.003.

6. Norman J.M., Handley S.A., Baldridge M.T., Droit L., Liu C.Y., Keller B.C. et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell. 2015;160(3):447–460. https://doi.org/10.1016/j.cell.2015.01.002.

7. Manrique P., Bolduc B., Walk S.T., Van Der Oost J., De Vos W.M., Young M.J. Healthy human gut phageome. Proc Natl Acad Sci. USA. 2016;113(37):10400–10405. https://doi.org/10.1073/pnas.1601060113.

8. Zuo T., Lu X.J., Zhang Y., Cheung C.P., Lam S., Zhang F. et al. Gut mucosal virome alterations in ulcerative colitis. Gut. 2019;68(7):1169–1179. https://doi.org/10.1136/gutjnl-2018-318131.

9. Lepage P., Colombet J., Marteau P., Sime-Ngando T., Doré J., LeClerc M. Dysbiosis in inflammatory bowel disease: a role for bacteriophages? Gut. 2008;57(3):424–425. https://doi.org/10.1136/gut.2007.134668.

10. Vishwakarma V., Periaswamy B., Bhusan Pati N., Slack E., Hardt W.D., Suar M. A novel phage element of Salmonella enterica serovar Enteritidis P125109 contributes to accelerated type III secretion system 2-dependent early inflammation kinetics in a mouse colitis model. Infect Immun. 2012;80(9):3236–3246. https://doi.org/10.1128/IAI.00180-12.

11. Wagner J., Maksimovic J., Farries G., Sim W.H., Bishop R.F., Cameron D.J. et al. Bacteriophages in gut samples from pediatric Crohn’s disease patients: metagenomic analysis using 454 pyrosequencing. Inflamm Bowel Dis. 2013;19(8):1598–1608. https://doi.org/10.1097/MIB.0b013e318292477c.

12. Watanabe R., Matsumoto T., Sano G., Ishii Y., Tateda K., Sumiyama Y. et al. Efficacy of bacteriophage therapy against gut-derived sepsis caused by Pseudomonas aeruginosa in mice. Antimicrob Agents Chemother. 2006;51(2):446–452. https://doi.org/10.1128/AAC.00635-06.

13. Meader E., Mayer M.J., Steverding D., Carding S.R., Narbad A. Evaluation of bacteriophage therapy to control Clostridium difficile and toxin production in an in vitro human colon model system. Anaerobe. 2013;(22):25–30. https://doi.org/10.1016/j.anaerobe.2013.05.001.

14. Sutton T.D.S., Hill C. Gut bacteriophage: current understanding and challenges. Front Endocrinol (Lausanne). 2019;(10):784. Available at: https://pubmed.ncbi.nlm.nih.gov/31849833/.

15. Myelnikov D. An alternative cure: the adoption and survival of bacteriophage therapy in the USSR, 1922–1955. J Hist Med Allied Sci. 2018;73(4):385–411. https://doi.org/10.1093/jhmas/jry024.

16. D’Hérelle F. Studies upon Asiatic cholera. Yale J Biol Med. 1929;1(4):195–219. Available at: https://pubmed.ncbi.nlm.nih.gov/21433426/.

17. Babalova E.G., Katsiladze K.T., Sakvarelidze L.A., Imnaishvili N.Sh., Sharashidze T.G., Badashvili V.A. Prophylactic doses of dry dysenteric bacteriophage. Zhurnal Mikrobiologii, Epidemiologii i Immunobiologii. 1968;(2):143–145. (In Russ.)

18. Kutter E., De Vos D., Gvasalia G., Alavidze Z., Gogokhia L., Kuh S., Abedon S.T. Phage therapy in clinical practice: treatment of human infections. Curr Pharm Biotechnol. 2010;11(1):69–86. https://doi.org/10.2174/138920110790725401.

19. Watkins R.R., Bonomo R.A. Overview: global and local impact of antibiotic resistance. Infect Dis Clin North Am. 2016;30(2):313–322. https://doi.org/10.1016/j.idc.2016.02.001.

20. Magiorakos A.P., Srinivasan A., Carey R.B., Carmeli Y., Falagas M.E., Giske C.G. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268–281. https://doi.org/10.1111/j.1469-0691.2011.03570.x.

21. Smirnov A.P., Shamkina P.A., Krivopalov A.A., Yanov Y.K., Shnajder N.A., Neznanov N.G. Personalized approach to the use of macrolides in the treatment of complicated forms of acute bacterial rhinosinusitis. Folia Otorhinolaryngologiae et Pathologiae Respiratoriae. 2019;25(3):60–72. (In Russ.) https://doi.org/10.33848/foliorl23103825-2019-25-3-60-72.

22. Zakharova I.N., Geppe N.A., Sugyan N.G., Denisova A.R., Berezhnaya I.V. Topical etiotropic drugs in the treatment of infectious and inflammatory diseases of the pharynx in preschool children. Results of a multicenter randomized comparative clinical trial. Rossiiskaya Otorinolaringologiya. 2021;20(1):102–117. (In Russ.) https://doi.org/10.18692/1810-4800-2021-1-102-117.

23. Aleshkin A.V. Historical review of the experience of using bacteriophages in Russia. Meditsinskiy Sovet. 2015;(7):12–17. (In Russ.) Available at: https://doi.org/10.21518/2079-701X-2015-7-12-17.

24. Cryan J.F., O’Riordan K.J., Sandhu K., Peterson V., Dinan T.G. The gut microbiome in neurological disorders. Lancet Neurol. 2020;19(2):179–194. https://doi.org/10.1016/S1474-4422(19)30356-4.

25. Glassner K.L., Abraham B.P., Quigley E.M.M. The microbiome and inflammatory bowel disease. J Allergy Clin Immunol. 2020;145(1):16–27. https://doi.org/10.1016/j.jaci.2019.11.003.

26. Markina A.N., Kapustina T.A., Parilova O.V., Belova E.V. Characteristics of biocenosis of nose and throat mucosa in patients with ENT pathology associated with chlamydia infection. Rossiiskaya Otorinolaringologiya. 2020;19(4):66–73. (In Russ.) https://doi.org/10.18692/1810-4800-2020-4-66-73.

27. Babaev S.Y., Novozhilov A.A., Abubakirov T.E., Mitrofanova N.N., Kozarenko E.A., Shahov A.V. Microbiota of the tympanic cavity in the patients with chronic suppurative otitis media. Rossiiskaya Otorinolaringologiya. 2019;18(3):22–26. (In Russ.) https://doi.org/10.18692/1810-4800-2019-3-22-26.

28. Lavrenova G.V., Kucherenko M.E. Restoration of an adequate microbial landscape of the mucous membrane of the ENT organs and intestines in order to treat and prevent chronic tonsillitis. Folia Otorhinolaryngologiae et Pathologiae Respiratoriae. 2018;24(3):101–111. (In Russ.) Available at: https://elibrary.ru/item.asp?id=36282452.

29. Shugakova E.V., Chaukina V.A., Kiselyov A.B., Avtushko A.S., Kiselyov V.V. Microbiocenosis of the upper respiratory tract as a risk factor for local complications of the postoperative period during extirpation of the larynx. Rossijskaya Otorinolaringologiya. 2017;(1):154–158. (In Russ.) Available at: https://www.entru.org/files/j_rus_LOR_1_2017_uv.pdf.

30. Breitbart M., Bonnain C., Malki K., Sawaya N.A. Phage puppet masters of the marine microbial realm. Nat Microbiol. 2018;3(7):754–766. https://doi.org/10.1038/s41564-018-0166-y.

31. De Sordi L., Lourenco M., Debarbieux L. “I will survive”: A tale of bacteriophage-bacteria coevolution in the gut. Gut Microbes. 2019;10(1):92–99. https://doi.org/10.1080/19490976.2018.1474322.

32. Fernandes M.A., Verstraete S.G., Phan T.G., Deng X., Stekol E., LaMere B. Enteric virome and bacterial microbiota in children with ulcerative colitis and crohn disease. J Pediatr Gastroenterol Nutr. 2019;68(1):30–36. Available at: https://journals.lww.com/jpgn/Fulltext/2019/01000/Enteric_Virome_and_Bacterial_Microbiota_in.8.aspx.

33. Van Belleghem J.D., Dąbrowska K., Vaneechoutte M., Barr J.J., Bollyky P.L. Interactions between Bacteriophage, Bacteria, and the Mammalian Immune System. Viruses. 2018;11(1):10. https://doi.org/10.3390/v11010010.

34. Torres-Barcelo C. The disparate effects of bacteriophages on antibioticresistant bacteria. Emerg Microbes Infect. 2018;7(1):168. https://doi.org/10.1038/s41426-018-0169-z.

35. Cold F., Olsen N.S., Djurhuus A.I.M.S.M., Hansen L.H. Bacteriophage therapy. Ugeskr Laeger. 2020;182(27):V01200041. Available at: https://pubmed.ncbi.nlm.nih.gov/32594993/.

36. Petrovic F.A, Lin R.C.Y., Ho J., Maddocks S., Ben Zakour N.L., Iredell J.R. et al. Safety of bacteriophage therapy in severe Staphylococcus aureus infection. Nat Microbiol. 2020;5(3):465–472. https://doi.org/10.1038/s41564-019-0634-z.

37. Cui Z., Guo X., Feng T., Li L. Exploring the whole standard operating procedure for phage therapy in clinical practice. J Transl Med. 2019;17(1):373. https://doi.org/10.1186/s12967-019-2120-z.

38. Dedrick R.M., Guerrero-Bustamante C.A., Garlena R.A., Russell D.A., Ford K., Harris K. et al. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat Med. 2019;25(5):730–733. https://doi.org/10.1038/s41591-019-0437-z.

39. Schooley R.T., Biswas B., Gill J.J., Hernandez-Morales A., Lancaster J., Lessor L. et al. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother. 2017;61(10):e00954–17. https://doi.org/10.1128/AAC.00954-17.

40. Aslam S., Courtwright A.M., Koval C., Lehman S.M., Morales S., Furr C.L. et al. Early clinical experience of bacteriophage therapy in 3 lung transplant recipients. Am J Transplant. 2019;19(9):2631–2639. https://doi.org/10.1111/ajt.15503.

41. Kim M., Jo Y., Hwang Y.J., Hong H.W., Hong S.S., Park K., Myung H. Phageantibiotic synergy via delayed lysis. Appl Environ Microbiol. 2018;84(22):02085–18. https://doi.org/10.1128/AEM.02085-18.

42. Bychinin M.V., Antonov I.O., Klypa T.V., Mandel’ I.A., Minec A.I., Kolyshkina N.A., Golobokova Y.B. Nosocomial infection in patients with severe and critical COVID-19. Obshchaya Reanimatologiya. 2022;18(1):4–10. (In Russ.) https://doi.org/10.15360/1813-9779-2022-1-4-10.

43. Kutsevalova O.Yu., Pokudina I.O., Rozenko D.A., Martynov D.V., Kaminsky M.Yu. Modern problems of antibiotic resistance gram-negative nosocomial infections in the Rostov region. Medical Herald of the South of Russia. 2019;10(3):91–96. (In Russ.) Available at: https://doi.org/10.21886/2219-8075-2019-10-3-.

44. Dolinnyj S.V., Kraeva L.A., Burgasova O.A., Ogarkova D.A. Assessment of clinical data and the species composition of pathogens in the upper respiratory tract of patients with COVID-19 and Determination of sensitivity to essential etiotropic drugs. Vrach. 2023;34(2):42–46. (In Russ.) Available at: https://vrachjournal.ru/ru/25877305-2023-02-09?ysclid=lg6dk6vh7b975866219.

45. Hvas C.L., Dahl Jørgensen S.M., Jørgensen S.P., Storgaard M., Lemming L., Hansen M.M. et al. Fecal microbiota transplantation is superior to fidaxomicin for treatment of recurrent Clostridium difficile infection. Gastroenterology. 2019;156(5):1324–1332.e3. https://doi.org/10.1053/j.gastro.2018.12.019.

46. Zuo T., Wong S.H., Lam K., Lui R., Cheung K., Tang W. et al. Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome. Gut. 2018;67(4):634–643. https://doi.org/10.1136/gutjnl-2017-313952.

47. Ott S.J., Waetzig G.H., Rehman A., Moltzau-Anderson J., Bharti R., Grasis J.A. et al. Efficacy of sterile fecal filtrate transfer for treating patients with Clostridium difficile infection. Gastroenterology. 2017;152(4):799–811.e7. https://doi.org/10.1053/j.gastro.2016.11.010.

48. Rasmussen T.S., Mentzel C.M.J., Kot W., Castro-Mejía J.L., Zuffa S., Swann J.R. et al. Faecal virome transplantation decreases symptoms of type 2 diabetes and obesity in a murine model. Gut. 2020;69(12):2122–2130. https://doi.org/10.1136/gutjnl-2019-320005.

49. Piletskaya U.V., Makarov K.Yu., Sokolova T.M. Evaluation of the efficacy of treatment regimens for bacterial vaginosis using bacteriophage gel. Farmakologiya & Farmakoterapiya. 2022;(1):104–107. (In Russ.) https://doi.org/10.46393/27132129_2022_1_104.

50. Zarochentseva N.V., Belaya Y.M. Experience of using phagogin gel in the therapy of non-specific vulvovaginitis. Issues of Practical Colposcopy. Genital Infections. 2022;(3):48–53. (In Russ.) https://doi.org/10.46393/27826392_2022_3_48.

51. Gerasimenko D.A., Sataeva T.P., Myasnikova O.N., Murynina P.V., Samtsova G.I., Ushakova E.Yu. et al. Prospects for phage therapy of the diseases caused by polyresistant strains of S. aureus. Tavricheskiy Mediko-Biologicheskiy Vestnik. 2022;25(2):170–177. (In Russ.) Available at: https://www.elibrary.ru/item.asp?id=49225664.

52. Rabinovich I.M., Gileva O.S., Akmalova G.M., Mannapova G.R., Epishova A.A., Gimranova I.A. Experience of using bacteriophages in the complex treatment of children with aphthous stomatitis. Stomatologiya. 2022;101(6):22–27. (In Russ.) https://doi.org/10.17116/stomat202210106122.

53. Chukhlyaev P.V., Khavkina D.A., Ruzhentsova T.A. Treatment of recurrent cystitis during the post-COVID-19 recovery: a case report. Academy of Medicine and Sports. 2021;2(2):27–30. (In Russ.) Available at: https://cyberleninka.ru/article/n/podhody-k-lecheniyuretsidiviruyuschego-tsistita-v-periode-rekonvalestsentsii-COVID-19.

54. Llorente C., Jepsen P., Inamine T., Wang L., Bluemel S., Wang H.J. et al. Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus. Nat Commun. 2017;8(1):837. https://doi.org/10.1038/s41467-017-00796-x.

55. Duan Y., Llorente C., Lang S., Brandl K., Chu H., Jiang L. et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature. 2019;575(7783):505–511. https://doi.org/10.1038/s41586-019-1742-x.

56. Kwiatek M., Parasion S., Nakonieczna A. Therapeutic bacteriophages as a rescue treatment for drug-resistant infections – an in vivo studies overview. J Appl Microbiol. 2020;128(4):985–1002. https://doi.org/10.1111/jam.14535.


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Nacharov PV, Krivopalov AA, Shustova TI. General characteristics, results and prospects for the clinical application of bacteriophage therapy. Meditsinskiy sovet = Medical Council. 2023;(7):170-175. (In Russ.) https://doi.org/10.21518/ms2023-106

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