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

Hang Zhang; Yifei Wei; Jiabao Xing; Yichao Zhang; Xinyu Sun; Zhuang Li; Yuying Zhang; Yushan Pan; Meng Zhang; Shanmei Wang; Yajun Zhai; Hua Wu

doi:10.1016/j.virs.2026.09.012

October 2026

Citation: Hang Zhang, Yifei Wei, Jiabao Xing, Yichao Zhang, Xinyu Sun, Zhuang Li, Yuying Zhang, Yushan Pan, Meng Zhang, Shanmei Wang, Yajun Zhai, Hua Wu. Epidemiology-guided discovery of a K1-specific lytic phage with therapeutic potential against ST23-K1 multidrug-resistant hypervirulent Klebsiella pneumoniae .VIROLOGICA SINICA, 2026, 41(5) : 1227-1242. http://dx.doi.org/10.1016/j.virs.2026.09.012

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

Hang Zhang ^a ,
Yifei Wei ^b ,
Jiabao Xing ^c ,
Yichao Zhang ^a ,
Xinyu Sun ^a ,
Zhuang Li ^a ,
Yuying Zhang ^a ,
Yushan Pan ^a ,
Meng Zhang ^d ,
Shanmei Wang ^e ,
Yajun Zhai ^{a
,,} ,
Hua Wu ^{a
,,}

a. Department of Pharmacology and Toxicology, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China;
b. Department of Clinical Laboratory, Henan University People's Hospital, Zhengzhou 450003, China;
c. School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai 200032, China;
d. Henan Centers for Disease Prevention and Control, Zhengzhou 450016, China;
e. Department of Clinical Microbiology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, China

Corresponding author: Yajun Zhai, zyj90518@126.com
Hua Wu, wuhua@henau.edu.cn
Received Date: 09 December 2025
Accepted Date: 24 September 2026
Available online: 28 September 2026

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 49,682nullbp 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.
- Klebsiella pneumoniae
- , MDR-KP
- , Genomic epidemiology
- , Phage therapy

Electronic Supplementary Material

10.1016j.virs.2026.09.012-ESM4.xlsx
10.1016j.virs.2026.09.012-ESM3.xlsx
10.1016j.virs.2026.09.012-ESM1.docx
10.1016j.virs.2026.09.012-ESM2.xlsx

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