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Peer-reviewedCC BY-NC-ND 4.0Virologica Sinica

Epidemiology-guided discovery of a K1-specific lytic phage with therapeutic potential against ST23-K1 multidrug-resistant hypervirulent Klebsiella pneumoniae

  • Hang Zhang1
  • Yifei Wei2
  • Jiabao Xing3
  • Yichao Zhang1
  • Xinyu Sun1
  • Zhuang Li1
  • Yuying Zhang1
  • Yushan Pan1
  • Meng Zhang4
  • Shanmei Wang5
  • Yajun Zhai1
  • Hua Wu1
5 affiliations
  1. 1Department of Pharmacology and Toxicology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China
  2. 2Department of Clinical Laboratory, Henan University People's Hospital, Zhengzhou 450003, China
  3. 3School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai 200032, China
  4. 4Henan Centers for Disease Prevention and Control, Zhengzhou 450016, China
  5. 5Department of Clinical Microbiology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, China
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Abstract

Phage therapy has emerged as a promising alternative for combating multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) infections. Recent advances suggest that tailoring phage cocktails based on genomic surveillance of circulating strains might yield more effective regimens (Koncz et al., 2024). Here, we combined publicly available epidemiological records with regional strain analysis to examine the distribution of the ST23-K1 lineage and to place the selected target in genomic and clinical context. Among the 227 isolates in our Henan collection, ST23-K1 accounted for 11.01% of isolates. We isolated a novel lytic phage, vB_KpnS_P10HW, from urban sewage using a clinically representative high-risk ST23-K1 MDR-hvKP strain, KH1127-5, as the host. vB_KpnS_P10HW exhibited lytic activity against K1-type K. pneumoniae isolates across four sequence types. The phage displayed rapid adsorption (80% within 10 min), a short latent period (5 min), and remarkable stability across temperature (4–60 °C) and pH (4–10) ranges. Whole-genome sequencing revealed a 49,682 bp linear dsDNA genome devoid of lysogeny, virulence, or antibiotic resistance genes. Phylogenomic analysis placed vB_KpnS_P10HW within the family Drexlerviridae, genus Webervirus. Functionally, vB_KpnS_P10HW rapidly reduced viable bacterial cells within 30 min at high multiplicities of infection and effectively disrupted preformed biofilms in a dose-dependent manner. In vivo, phage administration increased the survival rates in both Galleria mellonella and mouse infection models. These results support vB_KpnS_P10HW as a genetically safe and promising therapeutic candidate against clinically relevant ST23-K1-associated MDR-hvKP and suggest that integrating genomic epidemiological context with phage characterization may help prioritize regional targets for precision phage therapy against K. pneumoniae.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026epidemiologyguided,
  title = {{Epidemiology-guided discovery of a K1-specific lytic phage with therapeutic potential against ST23-K1 multidrug-resistant hypervirulent Klebsiella pneumoniae}},
  author = {Hang Zhang and Yifei Wei and Jiabao Xing and Yichao Zhang and Xinyu Sun and Zhuang Li and Yuying Zhang and Yushan Pan and Meng Zhang and Shanmei Wang and Yajun Zhai and Hua Wu},
  journal = {Virologica Sinica},
  year = {2026},
  month = sep,
  doi = {10.1016/j.virs.2026.09.012},
  url = {https://doi.org/10.1016/j.virs.2026.09.012},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Epidemiology-guided discovery of a K1-specific lytic phage with therapeutic potential against ST23-K1 multidrug-resistant hypervirulent Klebsiella pneumoniae
AU  - Hang Zhang
AU  - Yifei Wei
AU  - Jiabao Xing
AU  - Yichao Zhang
AU  - Xinyu Sun
AU  - Zhuang Li
AU  - Yuying Zhang
AU  - Yushan Pan
AU  - Meng Zhang
AU  - Shanmei Wang
AU  - Yajun Zhai
AU  - Hua Wu
PY  - 2026
DA  - 2026/09/28
JO  - Virologica Sinica
DO  - 10.1016/j.virs.2026.09.012
UR  - https://doi.org/10.1016/j.virs.2026.09.012
AB  - Phage therapy has emerged as a promising alternative for combating multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) infections. Recent advances suggest that tailoring phage cocktails based on genomic surveillance of circulating strains might yield more effective regimens (Koncz et al., 2024). Here, we combined publicly available epidemiological records with regional strain analysis to examine the distribution of the ST23-K1 lineage and to place the selected target in genomic and clinical context. Among the 227 isolates in our Henan collection, ST23-K1 accounted for 11.01% of isolates. We isolated a novel lytic phage, vB_KpnS_P10HW, from urban sewage using a clinically representative high-risk ST23-K1 MDR-hvKP strain, KH1127-5, as the host. vB_KpnS_P10HW exhibited lytic activity against K1-type K. pneumoniae isolates across four sequence types. The phage displayed rapid adsorption (80% within 10 min), a short latent period (5 min), and remarkable stability across temperature (4–60 °C) and pH (4–10) ranges. Whole-genome sequencing revealed a 49,682 bp linear dsDNA genome devoid of lysogeny, virulence, or antibiotic resistance genes. Phylogenomic analysis placed vB_KpnS_P10HW within the family Drexlerviridae, genus Webervirus. Functionally, vB_KpnS_P10HW rapidly reduced viable bacterial cells within 30 min at high multiplicities of infection and effectively disrupted preformed biofilms in a dose-dependent manner. In vivo, phage administration increased the survival rates in both Galleria mellonella and mouse infection models. These results support vB_KpnS_P10HW as a genetically safe and promising therapeutic candidate against clinically relevant ST23-K1-associated MDR-hvKP and suggest that integrating genomic epidemiological context with phage characterization may help prioritize regional targets for precision phage therapy against K. pneumoniae.
SN  - 1674-0769
SN  - 1995-820X
ER  -