Abstract
Klebsiella pneumoniae is a common pathogen responsible for various infections, with multidrug-resistant (MDR) strains increasingly complicating treatment. Phage therapy has shown significant potential in treating difficult bacterial infections; however, research specifically focused on phages targeting this bacterium remains limited. This study aimed to isolate and characterize lytic bacteriophages that target multidrug-resistant K. pneumoniae. Phages were isolated from 66 environmental samples through spot assays conducted on 10 multidrug-resistant strains. Phages were isolated via spot assays and purified via streak plating. Characterization included PCR-based identification and classification, determination of the latent period, efficiency of plating, burst size, stability testing, and evaluation of in vitro bactericidal activity. From a total of 660 spots tested against 10 multidrug-resistant (MDR) isolates, 102 phages were successfully isolated. These phages demonstrated individual lytic activity ranging from 8% (4/46) to 63% (29/46). PCR-based classification of the 60 bacteriophages identified six distinct virulent phage genera, with Taipeivirus being the most prevalent at 18.3% (11/60) and Webervirus the least common at 10.0% (6 out of 60). Stability assessments of pH and temperature demonstrated optimal activity between pH 5 and 9 and at temperatures up to 50 °C. These results endorse phage therapy as a viable alternative for treating MDR and hypervirulent K. pneumoniae infections. The data offer critical insights into local bacteriophage diversity and underscore its potential for developing targeted therapeutic agents. Genome sequencing, in vivo studies, and clinical trials are required to validate the efficacy and safety of these phages.
Data availability
All the data generated or analyzed during this study are included in this article and its supplementary information files.
References
Global burden of bacterial antimicrobial resistance. In 2019: a systematic analysis. Lancet 399 (10325), 629–655 (2022).
Effah, C. Y. et al. Klebsiella pneumoniae: an increasing threat to public health. Ann. Clin. Microbiol. Antimicrob. 19 (1), 1 (2020).
AAU. Black Lion Specialized Hospital (2025). https://hakimethio.org/facility/black-lion-specialized-hospital/).
Skurnik, M. et al. Phage therapy. Nat. Reviews Methods Primers. 5 (1), 9 (2025).
Hung, C. H. et al. Experimental phage therapy in treating Klebsiella pneumoniae-mediated liver abscesses and bacteremia in mice. Antimicrob. Agents Chemother. 55 (4), 1358–1365 (2011).
Cano, E. J. et al. Phage therapy for limb-threatening prosthetic knee Klebsiella pneumoniae infection: case report and in vitro characterization of anti-biofilm activity. Clin. Infect. Dis. 73 (1), e144–e151 (2021).
Martins, W. et al. Effective phage cocktail to combat the rising incidence of extensively drug-resistant Klebsiella pneumoniae sequence type 16. Emerg. Microbes Infect. 11 (1), 1015–1023 (2022).
Gan, L. et al. Bacteriophage effectively rescues pneumonia caused by prevalent multidrug-resistant Klebsiella pneumoniae in the early stage. Microbiol. Spectr. 10 (5), e0235822 (2022).
Broncano-Lavado, Antonio, et al. "Advances in bacteriophage therapy against relevant multidrug-resistant pathogens." Antibiotics 10.6 (2021): 672.
Li, Z. et al. Promising treatments for refractory pneumonia caused by multidrug-resistant Klebsiella pneumoniae. J. Drug Deliv. Sci. Technol. 87, 104874 (2023).
Conway, D., Mould, C. & Bewket, W. Over one century of rainfall and temperature observations in addis Ababa, Ethiopia. Int. J. Climatol. 24 (1), 77–91 (2004).
Shende, R. K. et al. Isolation and characterization of bacteriophages with lytic activity against common bacterial pathogens. Vet. World. 10 (8), 973–978 (2017).
Mkwata, H. M. et al. A laboratory practicum on screening for lytic bacteriophages from soil samples. Trans. Sci. Technol. 5 (4), 233–238 (2018).
Abebe, A. A., Birhanu, A. G. & Tessema, T. S. Isolation, purification, and phenotypic characterization of virulent Klebsiella pneumoniae phages from environmental samples in addis Ababa, ethiopia: A synergistic approach combining spot assay and streak plating. PLoS One. 20 (9), e0331955 (2025).
Salifu, S. P., Casey, S. C. & Foley, S. Isolation and characterization of soilborne virulent bacteriophages infecting the pathogen Rhodococcus equi. J. Appl. Microbiol. 114 (6), 1625–1633 (2013).
Suchithra, K. V. et al. Description and host-range determination of phage PseuPha1, a new species of pakpunavirus infecting multidrug-resistant clinical strains of Pseudomonas aeruginosa. Virology 585, 222–231 (2023).
Kutter, E. Phage host range and efficiency of plating. Methods Mol. Biol. 501, 141–149 (2009).
Naknaen, A. et al. Combination of genetically diverse Pseudomonas phages enhances the cocktail efficiency against bacteria. Sci. Rep. 13 (1), 8921 (2023).
Liu, J. et al. Isolation and characterization of bacteriophages against virulent Aeromonas hydrophila. BMC Microbiol. 20, 1–13 (2020).
Díaz-Galián, M. V., Vega-Rodríguez, M. A. & Molina, F. PhageCocktail: an R package to design phage cocktails from experimental phage-bacteria infection networks. Comput. Methods Programs Biomed. 221, 106865 (2022).
Jakočiūnė, D. & Moodley, A. A rapid bacteriophage DNA extraction method. Methods protocols. 1 (3), 27 (2018).
Kornienko, M. et al. PCR Assay for Rapid Taxonomic Differentiation of Virulent Staphylococcus aureus and Klebsiella pneumoniae Bacteriophages. Int. J. Mol. Sci. 24 (5), 4483 (2023).
Aghaee, B. L. et al. Sewage and sewage-contaminated environments are the most prominent sources to isolate phages against Pseudomonas aeruginosa. BMC Microbiol. 21, 1–8 (2021).
Williamson, K. E. et al. Viruses in soil ecosystems: an unknown quantity within an unexplored territory. Annual Rev. Virol. 4 (1), 201–219 (2017).
Fierer, N., Schimel, J. P. & Holden, P. A. Variations in microbial community composition through two soil depth profiles. Soil Biol. Biochem. 35 (1), 167–176 (2003).
Le Bris, J. et al. Phage therapy for Klebsiella pneumoniae: Understanding bacteria-phage interactions for therapeutic innovations. PLoS Pathog. 21 (4), e1012971 (2025).
Hyman & Abedon, S. T. Bacteriophage host range and bacterial resistance. Adv. Appl. Microbiol. 70, 217–248 (2010).
Dandekar, S. S. et al. Characterization of novel phages KPAФ1, KP149Ф1, and KP149Ф2 for lytic efficiency against clinical MDR Klebsiella pneumoniae infections. Microb. Pathog. 202, 107440 (2025).
Leshkasheli, L. et al. Klebsiella pneumoniae Phage M198 and Its Therapeutic Potential. Viruses 17 (1), 115 (2025).
Fang, Chengju, et al. "Isolation and characterization of three novel lytic phages against K54 serotype carbapenem-resistant hypervirulent Klebsiella pneumoniae." Frontiers in Cellular and Infection Microbiology 13 (2023): 1265011.
Townsend, E. M. et al. Isolation and characterization of Klebsiella phages for phage therapy. Phage (New Rochelle). 2 (1), 26–42 (2021).
Labrie, S. J., Samson, J. E. & Moineau, S. Bacteriophage resistance mechanisms. Nat. Rev. Microbiol. 8 (5), 317–327 (2010).
Whitfield, C. Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu. Rev. Biochem. 75 (1), 39–68 (2006).
Bertozzi Silva, J., Storms, Z. & Sauvageau, D. Host receptors for bacteriophage adsorption. FEMS Microbiol. Lett. 363 (4), fnw002 (2016).
Chen, H. et al. A Klebsiella-phage cocktail to broaden the host range and delay bacteriophage resistance both in vitro and in vivo. Npj Biofilms Microbiomes. 10 (1), 127 (2024).
Yoo, S. et al. Designing phage cocktails to combat the emergence of bacteriophage-resistant mutants in multidrug-resistant Klebsiella pneumoniae. Microbiol. Spectr. 12 (1), e0125823 (2024).
Geng, H. et al. Resistance of Klebsiella pneumoniae to phage hvKpP3 due to High-Molecular weight lipopolysaccharide synthesis failure. Microbiol. Spectr. 11 (3), e0438422 (2023).
Chen, C. et al. Isolation and characterization of novel bacteriophage vB_KpP_HS106 for Klebsiella pneumonia K2 and applications in foods. Front. Microbiol. 14, 1227147 (2023).
Mulani, M. S., Kumkar, S. N. & Pardesi, K. R. Characterization of novel Klebsiella phage PG14 and its antibiofilm efficacy. Microbiol. Spectr. 10 (6), e0199422 (2022).
Asif, M. et al. A K-17 serotype specific Klebsiella phage JKP2 with biofilm reduction potential. Virus Res. 329, 199107 (2023).
Ananna, N. T. et al. Characterization of two lytic bacteriophages infecting carbapenem-resistant clinical Klebsiella pneumoniae in Dhaka, Bangladesh. Virus Res. 350, 199491 (2024).
Mourali, D. et al. Isolation and characterization of lytic phages infecting clinical Klebsiella pneumoniae from tunisia. Antibiotics 13 (12), 1154 (2024).
Uskudar-Guclu, A. et al. Biological and genomic characteristics of three novel bacteriophages and a phage-plasmid of Klebsiella pneumoniae. Can. J. Microbiol. 70 (6), 213–225 (2024).
Feng, J. et al. Characterization and genome analysis of phage vB_KpnS_SXFY507 against Klebsiella pneumoniae and efficacy assessment in galleria Mellonella larvae. Front. Microbiol. 14, 1081715 (2023).
Lin, T. L. et al. Isolation of a bacteriophage and its depolymerase specific for K1 capsule of Klebsiella pneumoniae: implication in typing and treatment. J. Infect. Dis. 210 (11), 1734–1744 (2014).
Abedon, S. T., Herschler, T. D. & Stopar, D. Bacteriophage latent-period evolution as a response to resource availability. Appl. Environ. Microbiol. 67 (9), 4233–4241 (2001).
Abedon, S. T., Hyman & Thomas, C. Experimental examination of bacteriophage latent-period evolution as a response to bacterial availability. Appl. Environ. Microbiol. 69 (12), 7499–7506 (2003).
Sada, T. S. & Tessema, T. S. Isolation and characterization of lytic bacteriophages from various sources in addis Ababa against antimicrobial-resistant diarrheagenic Escherichia coli strains and evaluation of their therapeutic potential. BMC Infect. Dis. 24 (1), 310 (2024).
Li, P. et al. Characteristics of a Bacteriophage, vB_Kox_ZX8, isolated from clinical Klebsiella Oxytoca and its therapeutic effect on mice bacteremia. Front. Microbiol. 12, 763136 (2021).
Saqr, E. et al. Analysis of a new phage, KZag1, infecting biofilm of Klebsiella pneumoniae: genome sequence and characterization. BMC Microbiol. 24 (1), 211 (2024).
Abusalah, M. et al. Isolation and characterization of bacteriophage against clinical isolates of AmpC beta lactamase-Producing Klebsiella pneumoniae from hospital wastewater. PLoS One. 20 (2), e0315079 (2025).
Peng, Qin, et al. Characterization of bacteriophage vB_KleM_KB2 possessing high control ability to pathogenic Klebsiella pneumoniae. Scientific Reports 13(1), 9815 (2023).
Sae-Ueng, U. et al. Nanomechanical resilience and thermal stability of RSJ2 phage. Sci. Rep. 14 (1), 19389 (2024).
Caflisch, K. M., Suh, G. A. & Patel, R. Biological challenges of phage therapy and proposed solutions: a literature review. Expert Rev. Anti Infect. Ther. 17 (12), 1011–1041 (2019).
Jończyk, E. et al. The influence of external factors on bacteriophages–review. Folia Microbiol. (Praha). 56 (3), 191–200 (2011).
Elsayed, M. M. et al. Isolation and encapsulation of bacteriophage with Chitosan nanoparticles for biocontrol of multidrug-resistant methicillin-resistant Staphylococcus aureus isolated from broiler poultry farms. Sci. Rep. 14 (1), 4702 (2024).
Ahmadi, H. et al. Thermal-stability and reconstitution ability of Listeria phages P100 and A511. Front. Microbiol. 8, 2375 (2017).
Das, S. & Kaledhonkar, S. Physiochemical characterization of a potential Klebsiella phage MKP-1 and analysis of its application in reducing biofilm formation. Front. Microbiol. 15, 1397447 (2024).
Baqer, A. A. et al. In vitro activity, stability and molecular characterization of eight potent bacteriophages infecting carbapenem-resistant Klebsiella pneumoniae. Viruses 15 (1), 117 (2022).
Tremblay, D., Moineau, S. & Ackermann, H. W. Long-term bacteriophage preservation. (2004).
Li, J. et al. Ackermannviridae bacteriophage against carbapenem-resistant Klebsiella pneumoniae of capsular type 64. Front. Microbiol. 15, 1462459 (2024).
Ichikawa, M. et al. Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis. Nat. Commun. 14 (1), 3261 (2023).
Hesse, S. et al. Phage resistance in multidrug-resistant Klebsiella pneumoniae ST258 evolves via diverse mutations that culminate in impaired adsorption. MBio 11(1), 10–1128 (2020).
Abbas, S. et al. Bacteriophage therapy: a possible alternative therapy against antibiotic-resistant strains of Klebsiella pneumoniae. Front. Microbiol. 16, 1443430 (2025).
Ponsecchi, G. et al. Characterization of four novel bacteriophages targeting multi-drug resistant Klebsiella pneumoniae strains of sequence type 147 and 307. Front. Cell. Infect. Microbiol. 14, 1473668 (2024).
Ballesté, E. et al. Bacteriophages in sewage: abundance, roles, and applications. FEMS Microbes. 3, xtac009 (2022).
Hyman, P. Phages for phage therapy: isolation, characterization, and host range breadth. Pharmaceuticals 12(1), 35 (2019).
Alharbi, N. M. & Ziadi, M. M. Wastewater as a fertility source for novel bacteriophages against multi-drug resistant bacteria. Saudi J. Biol. Sci. 28 (8), 4358–4364 (2021).
Martins, W. et al. Diversity of lytic bacteriophages against XDR Klebsiella pneumoniae sequence type 16 recovered from sewage samples in different parts of the world. Sci. Total Environ. 839, 156074 (2022).
Koskella, B. & Brockhurst, M. A. Bacteria-phage Coevolution as a driver of ecological and evolutionary processes in microbial communities. FEMS Microbiol. Rev. 38 (5), 916–931 (2014).
Author information
Authors and Affiliations
Contributions
AAA: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing -original draft, Writing - review & editing AGB: Conceptualization, Validation, Writing -review & editingTST: Conceptualization, Funding acquisition, Project administration, Resources, Validation, Writing – review & editing.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethical clearance
The study proposal was reviewed and approved by the Research Ethics Committee at the Institute of Biotechnology, Addis Ababa University (IoB/431/2016/2024). All methods were carried out in accordance with relevant ethical guidelines and regulations.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Abebe, A.A., Birhanu, A.G. & Tessema, T.S. Isolation and characterization of lytic bacteriophages with therapeutic potential against multidrug resistant Klebsiella pneumoniae from Ethiopia. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39153-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-026-39153-8