{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:15:53Z","timestamp":1793171753325,"version":"4.5.0"},"reference-count":26,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2019-1671"],"award-info":[{"award-number":["075-15-2019-1671"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: The emergence of multidrug-resistant hypervirulent Klebsiella pneumoniae (hvKp) has made it difficult to treat and control infections caused by this bacterium. Previously, the therapeutic effectiveness of phage-encoded depolymerase Dep_kpv74 in a mouse model of K. pneumoniae-induced thigh soft tissue infection was reported. In this study, the effect of Dep_kpv74 on blood parameters in mice, the proliferation and subpopulation composition of spleen lymphocytes, and the activity and stability of the enzyme at different pH and temperatures were further explored. Results: The stability tests showed that Dep_kpv74 remained active in the temperature range from 8 \u00b0C to 55 \u00b0C. The optimal pH value for maintaining the activity of Dep_kpv74 ranged from 5.0 to 9.0. The depolymerase was detected in the blood, spleen, and lungs of mice 10 min after intraperitoneal administration, reaching maximum activity values after 1\u20133 h and maintaining activity a day after administration. The introduction of Dep_kpv74 at the therapeutic dose (10 \u03bcg\/mouse) or at a 10-fold higher dose did not lead to reliable changes in bloodstream cell content compared with the reference values of intact mice. The biochemical results of the studies indicated that Dep_kpv74 did not exert any toxic effects on liver and kidney functions. The results of the analysis of lymphocyte proliferative activity demonstrated that Dep_kpv74 depolymerase has a mild immunomodulatory effect. Conclusions: Thus, the results of this study provide one more confirmation that depolymerase Dep_kpv74 is a potential candidate for the treatment of infections caused by hvKp expressing K2 capsular polysaccharides.<\/jats:p>","DOI":"10.3390\/antibiotics14010044","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T03:38:41Z","timestamp":1736221121000},"page":"44","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunomodulatory Effect of Phage Depolymerase Dep_kpv74 with Therapeutic Potential Against K2-Hypervirulent Klebsiella pneumoniae"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4667-1451","authenticated-orcid":false,"given":"Nikolay V.","family":"Volozhantsev","sequence":"first","affiliation":[{"name":"State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Makarova","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena S.","family":"Kartseva","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina V.","family":"Silkina","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina M.","family":"Krasilnikova","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-192X","authenticated-orcid":false,"given":"Egor A.","family":"Denisenko","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6309-7645","authenticated-orcid":false,"given":"Alexander I.","family":"Borzilov","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria V.","family":"Firstova","sequence":"additional","affiliation":[{"name":"State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4161\/viru.22718","article-title":"Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: A new and dangerous breed","volume":"4","author":"Shon","year":"2013","journal-title":"Virulence"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/joim.13007","article-title":"Hypervirulent Klebsiella pneumoniae-clinical and molecular perspectives","volume":"287","author":"Choby","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1086\/519424","article-title":"Invasive Klebsiella pneumoniae syndrome in North America","volume":"45","author":"Nadasy","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1099\/jmm.0.46964-0","article-title":"Genetically similar isolates of Klebsiella pneumoniae serotype K1 causing liver abscesses in three continents","volume":"56","author":"Turton","year":"2007","journal-title":"J. Med. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6115","DOI":"10.1128\/AAC.01127-16","article-title":"High Prevalence of Hypervirulent Klebsiella pneumoniae Infection in China: Geographic Distribution, Clinical Characteristics, and Antimicrobial Resistance","volume":"60","author":"Zhang","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lee, C.R., Lee, J.H., Park, K.S., Jeon, J.H., Kim, Y.B., Cha, C.J., Jeong, B.C., and Lee, S.H. (2017). Antimicrobial resistance of hypervirulent Klebsiella pneumoniae: Epidemiology, hypervirulence-associated determinants, and resistance mechanisms. Front. Cell Infect. Microbiol., 21.","DOI":"10.3389\/fcimb.2017.00483"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1128\/MMBR.00078-15","article-title":"Klebsiella pneumoniae: Going on the Offense with a Strong Defense","volume":"80","author":"Paczosa","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1128\/IAI.70.5.2583-2590.2002","article-title":"Molecular analysis of the contribution of the capsular polysaccharide and the lipopolysaccharide O side chain to the virulence of Klebsiella pneumoniae in a murine model of pneumonia","volume":"70","author":"Cortes","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1128\/iai.62.10.4495-4499.1994","article-title":"Polysaccharide capsule-mediated resistance to opsonophagocytosis in Klebsiella pneumoniae","volume":"62","author":"Domenico","year":"1994","journal-title":"Infect. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1007\/s00253-017-8224-6","article-title":"Bacteriophage-encoded virion associated enzymes to overcome the carbohydrate barriers during the infection process","volume":"101","author":"Latka","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1007\/s00253-015-7247-0","article-title":"Bacteriophage-encoded depolymerases: Their diversity and biotechnological applications","volume":"100","author":"Pires","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Brzozowska, E., Pyra, A., Pawlik, K., Janik, M., G\u00f3rska, S., Urbanska, N., Drulis-Kawa, Z., and Gamian, A. (2017). Hydrolytic activity determination of Tail Tubular Protein A of Klebsiella pneumoniae bacteriophages towards saccharide substrates. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-18096-1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1093\/infdis\/jiu332","article-title":"Isolation of a bacteriophage and its depolymerase specific for K1 capsule of Klebsiella pneumoniae: Implication in typing and treatment","volume":"210","author":"Lin","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Majkowska-Skrobek, G., \u0141\u0105tka, A., Berisio, R., Maciejewska, B., Squeglia, F., Romano, M., Lavigne, R., Struve, C., and Drulis-Kawa, Z. (2016). Capsule-Targeting Depolymerase, Derived from Klebsiella KP36 Phage, as a Tool for the Development of Anti-Virulent Strategy. Viruses, 8.","DOI":"10.3390\/v8120324"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Majkowska-Skrobek, G., Latka, A., Berisio, R., Squeglia, F., Maciejewska, B., Briers, Y., and Drulis-Kawa, Z. (2018). Phage-Borne depolymerases decrease Klebsiella pneumoniae resistance to innate defense mechanisms. Front. Microbiol., 23.","DOI":"10.3389\/fmicb.2018.02517"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hsieh, P.F., Lin, H., Lin, T.L., Chen, Y.Y., and Wang, J.T. (2017). Two T7-like Bacteriophages, K5-2 and K5-4, Each Encodes Two Capsule Depolymerases: Isolation and Functional Characterization. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-04644-2"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Volozhantsev, N.V., Shpirt, A.M., Borzilov, A.I., Komisarova, E.V., Krasilnikova, V.M., Shashkov, A.S., Verevkin, V.V., and Knirel, Y.A. (2020). Characterization and Therapeutic Potential of Bacteriophage-Encoded Polysaccharide Depolymerases with \u03b2 Galactosidase Activity against Klebsiella pneumoniae K57 Capsular Type. Antibiotics, 9.","DOI":"10.3390\/antibiotics9110732"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"198951","DOI":"10.1016\/j.virusres.2022.198951","article-title":"Comparison of the therapeutic potential of bacteriophage KpV74 and phage-derived depolymerase (\u03b2-glucosidase) against Klebsiella pneumoniae capsular type K2","volume":"322","author":"Volozhantsev","year":"2022","journal-title":"Virus Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gorodnichev, R.B., Volozhantsev, N.V., Krasilnikova, V.M., Bodoev, I.N., Kornienko, M.A., Kuptsov, N.S., Popova, A.V., Makarenko, G.I., Manolov, A.I., and Slukin, P.V. (2021). Novel Klebsiella pneumoniae K23-Specific Bacteriophages From Different Families: Similarity of Depolymerases and Their Therapeutic Potential. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.669618"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/0042-6822(73)90293-6","article-title":"A bacteriophage-induced depolymerase active on Klebsiella K11 capsular polysaccharide","volume":"56","author":"Bessler","year":"1973","journal-title":"Virology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wu, Y., Wang, R., Xu, M., Liu, Y., Zhu, X., Qiu, J., Liu, Q., He, P., and Li, Q. (2019). A Novel Polysaccharide Depolymerase Encoded by the Phage SH-KP152226 Confers Specific Activity Against Multidrug-Resistant Klebsiella pneumoniae via Biofilm Degradation. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2019.02768"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100737","DOI":"10.1016\/j.curtheres.2024.100737","article-title":"Biomarkers of Hepatic Toxicity: An Overview","volume":"26","author":"Thakur","year":"2024","journal-title":"Curr. Ther. Res. Clin. Exp."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s11626-013-9705-2","article-title":"Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule","volume":"50","author":"Ando","year":"2014","journal-title":"In Vitro Cell Dev. Biol. Anim."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/j.1365-2567.2008.02832.x","article-title":"The modulatory effects of lipopolysaccharide-stimulated B cells on differential T-cell polarization","volume":"125","author":"Xu","year":"2008","journal-title":"Immunology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1002\/eji.201646837","article-title":"CD69: From activation marker to metabolic gatekeeper","volume":"47","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.virusres.2017.09.026","article-title":"Comparative genome analysis of novel Podoviruses lytic for hypermucoviscous Klebsiella pneumoniae of K1, K2, and K57 capsular types","volume":"243","author":"Solovieva","year":"2018","journal-title":"Virus Res."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/1\/44\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:23:58Z","timestamp":1759919038000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/1\/44"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["antibiotics14010044"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14010044","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]}}}