INFLUENCE OF THE DRUG FAGOMAST ON THE VITAL ACTIVITY OF CILIATES AND THE MUCOUS MEMBRANE OF THE EYES OF RABBITS
Keywords:bacteriophage drug Fagomast, ciliate, Tetrachymena pyriformis, toxicity, irritating effect
Phage therapy is an alternative in the treatment of bacterial infections caused by antibiotic-resistant strains of bacteria, including mastitis in cows. Bacteriophage-based drugs for the treatment of mastitis in cows shall comply with the standards usually applied to pharmaceutical products. The aim of the work is to investigate the effect of the phage drug Fagomast on the vital activity of the ciliate Tetrachymena pyriformis and its possible irritating effect on the mucous membrane of the eyes of rabbits. For this purpose, a certified museum strain of the ciliate Tetrachymena pyriformis WH-14 has been used in accordance with generally accepted recommendations. To sterile test tubes with drug solutions has been added 0.05 ml of a 72-hour ciliate culture. After 0.5, 1 and 96 hours microscopy has been performed: the number of ciliates in the Goryaev chamber has been counted and their mobility has been determined. Each dilution of the drug has been studied in triplicate. Evaluation of the harmful (irritating) effect of phage drug solutions on the mucous membrane of the eyes of rabbits has been performed in accordance with all bioethical standards of animal handling. Each concentration of the drug has been instilled 2-3 drops into the conjunctival sac of one eye of the rabbit, and the other eye has been served as a control. The drug has been applied twice a day for 5 days. According to the results of research, it has been found that at the concentration of phages from 104 to 109 PFU/ml in the drug there is no change in motor activity and pathological abnormalities in the cells of ciliates. When determining the local irritating effect of Fagomast on the mucous membranes of the eyes of a rabbit, no visible changes have been observed both for the applying of the drug in the amount of phage parts of 104 PFU/ml and at the maximum content of 109 PFU/ml. Therefore, toxicological studies have shown that the bacteriophage-based drug Fagomast developed by us for the treatment of mastitis in cows can be recommended for further production tests.
Le Maréchal, C., Thiéry, R., Vautor, E., & Le Loir, Y. (2011). Mastitis impact on technological properties of milk and quality of milk products—a review. Dairy Science & Technology, 91(3), 247-282. https://doi.org/10.1007/s13594-011-0009-6
Detilleux, J. (2018). Tolerance to bovine clinical mastitis: Total, direct, and indirect milk losses. Journal of dairy science, 101(4), 3334-3343. https://doi.org/10.3168/jds.2017-13976
Bogni, C., Odierno, L., Raspanti, C., Giraudo, J., Larriestra, A., Reinoso, E., & Vissio, C.(2011). War against mastitis: Current concepts on controlling bovine mastitis pathogens. Science against microbial pathogens: Communicafing current research and technological advances, 483-494.
Leitner, L., Ujmajuridze, A., Chanishvili, N., Goderdzishvili, M., Chkonia, I., Rigvava, S., & Kessler, T.M. (2021). Intravesical bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: A randomised, placebo-controlled, double-blind clinical trial. The Lancet Infectious Diseases, 21(3), 427-436. https://doi.org/10.1016/S1473-3099(20)30330-3.
Alves, D. R., Gaudion, A., Bean, J. E., Perez Esteban, P., Arnot, T. C., Harper, D. R., & Jenkins, A. T. A. (2014). Combined use of bacteriophage K and a novel bacteriophage to reduce Staphylococcus aureus biofilm formation. Applied and Environmental Microbiology, 80(21), 6694-6703. https://doi.org/10.1128/AEM.01789-14
Horiuk, Y. V. (2018). Fagotherapy of cows mastitis as an alternative to antibiotics in the system of obtaining environmentally safe milk. Scientific Messenger of Lviv National University of Veterinary Medicine and Biotechnologies, 20(88), 42–47. https://doi.org/10.32718/nvlvet8807
Düzgüneş, N., Sessevmez, M., & Yildirim, M. (2021). Bacteriophage therapy of bacterial infections: The rediscovered frontier. Pharmaceuticals, 14(1), 1-16. https://doi.org/10.3390/ph14010034
Mutti, M., & Corsini, L. (2019). Robust approaches for the production of active ingredient and drug product for human phage therapy. Frontiers in microbiology, 10, 2289. https://doi.org/10.3389/fmicb.2019.02289
Fauconnier, A. (2019). Phage therapy regulation: from night to dawn. Viruses, 11(4), 1-8. https://doi.org/10.3390/v11040352
Fauconnier, A. Regulating phage therapy: (2017). The biological master file concept could help to overcome regulatory challenge of personalized medicines. EMBO Rep, 18, 198–200. https://doi.org/10.15252/embr.201643250.
Verbeken, G., Pirnay, J.-P., De Vos, D., Jennes, S., Zizi, M., Lavigne, R., & Huys, I. (2012). Optimizing the European Regulatory Framework for Sustainable Bacteriophage Therapy in Human Medicine. Arch. Immunol. Ther. Exp, 60, 161–172. https://doi.org/10.1007/s00005-012-0175-0.
Horiuk, Y. V., Kukhtyn, M. D., Stravskyy, Y. S., Klymnyuk, S. I., Vergeles, K. M., & Horiuk, V. V. (2019). Influence of staphylococcal phage SAvB14 on biofilms, formed by Staphylococcus aureus variant bovis. Regulatory Mechanisms in Biosystems, 10(3), 314-318. https://doi.org/10.15421/021948.
Lemesh, V.M., Pakhomov, P.I., Yanchenko, A.Ye., Titova, L.G., & Anisimova, N.N. (1997). Metodicheskie ukazaniya po toksiko-biologicheskoy otsenke myasa, myasnykh produktov i moloka s ispolzovaniem infuzorii Tetrakhimeny periformis (ekspress-metod) [Methodical instructions for toxic biological evaluation of meat, meat products and milk using infusoria Tetrachimenes periformis (express method)] Guidelines. Vitebsk: Vitebskaya gos.akad.vet.med. i Belorusskaya nauch.-issled. inst. eksper.
veterinarii (in Russian).
Kotsiumbas, I. Ya., Malyk, O. H., & Patereha, I. P. (2006). Doklinichni doslidzhennia veterynarnykh likarskykh zasobiv. Lviv: Triada plius. (in Ukrain).
Kwiatek, M., Parasion, S., Mizak, L., Gryko, R., Bartoszcze, M., & Kocik, J. (2012). Characterization of a bacteriophage, isolated from a cow with mastitis, that is lytic against Staphylococcus aureus strains. Archives of virology, 157(2), 225-234. https://doi.org/10.1007/s00705-011-1160-3.
Li, L., & Zhang, Z. (2014). Isolation and characterization of a virulent bacteriophage SPW specific for Staphylococcus aureus isolated from bovine mastitis of lactating dairy cattle. Molecular biology reports, 41(9), 5829-5838. https://doi.org/10.1007/s11033-014-3457-2
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