Improvement of phage therapy based on methods of non-directional accelerated evolution of bacteriophages
A. M. Nifontova,
A. N. Gorshkov,
N. E. Gyulikhandanova,
O. V. Shneider,
B. I. Aslanov,
A. E. Goncharov,
D. A. Lioznov https://doi.org/10.24884/1607-4181-2025-32-4-37-44
Abstract
Bacterial resistance to antimicrobials is one of the actual medical problems that require urgent solutions. The severity of the course of infectious diseases caused by multidrug-resistant bacteria is an impetus for the search for other treatment options, in particular, the use of bacteriophages as antimicrobial agents. Potentially, phage therapy can be used both as an addition to antibiotics and as a substitute for the latter. However, isolation of a native bacteriophage is a laborious and time-consuming process. In addition, during the interaction of bacteria and phages, bacterial defense mechanisms develop, aimed at evading phage exposure. The use of accelerated evolution technologies based on changing the genotypes of bacteriophages may be a solution to this problem. Viruses obtained in this way can have unique properties that help not only overcome bacterial resistance mechanisms, but also expand the range of lytic activity, which makes it possible to use them even in conditions of constant bacterial evolution. In addition, new mutations can improve the stability of phages when they are stored as drugs for phage therapy. In general, accelerated evolution technologies, including Appelman protocol recombination, chemical and thermal mutagenesis, modification of phages using ultraviolet radiation, and phage and bacterial coevolution procedures, are affordable and relatively inexpensive, but at the same time effective methods for converting phage genomes to expand the possibilities of using bacteriophages in medical practice.
Keywords
phage therapy,
accelerated evolution,
Appelman’s protocol,
chemical mutagenesis,
undirected bacteriophage evolution
Supporting agencies: The research was carried out at the expense of a grant from the Russian Science Foundation № 24-15-20022, https://rscf.ru/project/24-15-20022, and at the expense of a grant from the Saint Petersburg Science Foundation № 24-15-20022.
About the Authors
A. M. Nifontova
Smorodintsev Research Institute of Influenza
Russian Federation
Competing Interests:
Russian Federation
Nifontova Anna M., Postgraduate Student
15/17, Professor Popov str., Saint-Petersburg, 197376
Competing Interests:
Authors declare no conflict of interest.
A. N. Gorshkov
Smorodintsev Research Institute of Influenza
Russian Federation
Competing Interests:
Russian Federation
Gorshkov Andrey N., Cand. of Sci. (Biol.), Leading Research Fellow, Department of Biotechnology
15/17, Professor Popov str., Saint-Petersburg, 197376
Competing Interests:
Authors declare no conflict of interest.
N. E. Gyulikhandanova
Smorodintsev Research Institute of Influenza
Russian Federation
Competing Interests:
Russian Federation
Gyulikhandanova Natalia E., Deputy Director for R&D
15/17, Professor Popov str., Saint-Petersburg, 197376
Competing Interests:
Authors declare no conflict of interest.
O. V. Shneider
Smorodintsev Research Institute of Influenza
Russian Federation
Competing Interests:
Russian Federation
Shneider Olga V., Cand. of Sci. (Med.), Head of the Clinical Diagnostic Laboratory – Clinical Laboratory Diagnostics Ddoctor
15/17, Professor Popov str., Saint-Petersburg, 197376
Competing Interests:
Authors declare no conflict of interest.
B. I. Aslanov
Smorodintsev Research Institute of Influenza; North-Western State Medical University named after I. I. Mechnikov
Russian Federation
Competing Interests:
Russian Federation
Aslanov Batyrbek I., Dr. Sci. (Med.), Professor, Head of the Department of Epidemiology, Parasitology and Disinfection, Head of the Laboratory of Molecular Epidemiology and
Bacteriophage Research
15/17, Professor Popov str., Saint-Petersburg, 197376;
47, Piskarevsky pr., Saint Petersburg, 195067
Competing Interests:
Authors declare no conflict of interest.
A. E. Goncharov
Smorodintsev Research Institute of Influenza; North-Western State Medical University named after I. I. Mechnikov
Russian Federation
Competing Interests:
Russian Federation
Goncharov Artemiy E., Dr. Sci. (Med.), Professor, Department of Epidemiology, Parasitology and Disinfection, Leading Research Fellow of the Laboratory of Molecular Epidemiology and Bacteriophage Research
15/17, Professor Popov str., Saint-Petersburg, 197376;
47, Piskarevsky pr., Saint Petersburg, 195067
Competing Interests:
Authors declare no conflict of interest.
D. A. Lioznov
Smorodintsev Research Institute of Influenza; Pavlov University
Russian Federation
Competing Interests:
Russian Federation
Lioznov Dmitry A., Dr. Sci. (Med.), Professor, Director, Smorodintsev Research Institute of Influenza, Head of the Department of Infectious Diseases and Epidemiology
15/17, Professor Popov str., Saint-Petersburg, 197376;
6-8, L’va Tolstogo str., Saint Petersburg, 197022
Competing Interests:
Authors declare no conflict of interest.
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For citations:
Nifontova A.M., Gorshkov A.N., Gyulikhandanova N.E., Shneider O.V., Aslanov B.I., Goncharov A.E., Lioznov D.A. Improvement of phage therapy based on methods of non-directional accelerated evolution of bacteriophages. The Scientific Notes of the Pavlov University. 2025;32(4):37-44. (In Russ.) https://doi.org/10.24884/1607-4181-2025-32-4-37-44
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