Genomic surveillance-guided phage repository construction and rational cocktail design for carbapenem-resistant
5 affiliations
- 1National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, Hubei 430070, China
- 2College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China
- 3College of Chemistry, Huazhong Agricultural University, Wuhan, Hubei 430070, China
- 4National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China
- 5Faculty of Public Health, Kasetsart University, Chalermphrakiat Sakon Nakhon Province Campus, Sakon Nakhon 47000, Thailand
Abstract
Objectives: Given the treatment delays inherent in reactive phage matching, we aimed to develop a preparedness-oriented strategy linking genomic surveillance of carbapenem-resistant Klebsiella pneumoniae (CRKP) to targeted phage-resource development and rational cocktail design. Methods: We analysed >64,000 K. pneumoniae genomes to characterize the geographical and temporal representation of KL types within the genomic dataset. Phages were isolated and prioritized according to host-range profiles, genomic nonredundancy, receptor-binding protein diversity and morphology. Quantitative inhibition profiling and principal component analysis guided the selection of candidate combinations targeting KL64 isolates, followed by in vitro , in vivo, and resistance analyses. Results: A limited number of KL types were frequently represented among the analysed CRKP genomes and showed regional variation. From a nonredundant repository of 33 phages, 10 were selected to target 10 frequently represented KL types. In a KL64 clinical isolate panel, selected combinations broadened and prolonged bacterial suppression. The phage cocktail significantly prolonged survival in mice under lethal CRKP challenge and phage-resistant derivatives showed restored susceptibility to multiple antibiotics. Conclusions: This study presents a framework for using genomic data to prioritize phage-resource development and guide cocktail design for KL-defined CRKP groups.
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BibTeX
@article{lei2026genomic,
title = {{Genomic surveillance-guided phage repository construction and rational cocktail design for carbapenem-resistant}},
author = {Miao Lei and Haoyu Guo and Yanzhang Guo and Mengdi Cui and Xing Ding and Shan Wang and Anusak Kerdsin and Ranfeng Ye and Jinquan Li},
journal = {Journal of Infection},
year = {2026},
month = oct,
doi = {10.1016/j.jinf.2026.106882},
url = {https://doi.org/10.1016/j.jinf.2026.106882},
note = {CC BY},
}
RIS
TY - JOUR
TI - Genomic surveillance-guided phage repository construction and rational cocktail design for carbapenem-resistant
AU - Miao Lei
AU - Haoyu Guo
AU - Yanzhang Guo
AU - Mengdi Cui
AU - Xing Ding
AU - Shan Wang
AU - Anusak Kerdsin
AU - Ranfeng Ye
AU - Jinquan Li
PY - 2026
DA - 2026/10/30
JO - Journal of Infection
DO - 10.1016/j.jinf.2026.106882
UR - https://doi.org/10.1016/j.jinf.2026.106882
AB - Objectives: Given the treatment delays inherent in reactive phage matching, we aimed to develop a preparedness-oriented strategy linking genomic surveillance of carbapenem-resistant Klebsiella pneumoniae (CRKP) to targeted phage-resource development and rational cocktail design. Methods: We analysed >64,000 K. pneumoniae genomes to characterize the geographical and temporal representation of KL types within the genomic dataset. Phages were isolated and prioritized according to host-range profiles, genomic nonredundancy, receptor-binding protein diversity and morphology. Quantitative inhibition profiling and principal component analysis guided the selection of candidate combinations targeting KL64 isolates, followed by in vitro , in vivo, and resistance analyses. Results: A limited number of KL types were frequently represented among the analysed CRKP genomes and showed regional variation. From a nonredundant repository of 33 phages, 10 were selected to target 10 frequently represented KL types. In a KL64 clinical isolate panel, selected combinations broadened and prolonged bacterial suppression. The phage cocktail significantly prolonged survival in mice under lethal CRKP challenge and phage-resistant derivatives showed restored susceptibility to multiple antibiotics. Conclusions: This study presents a framework for using genomic data to prioritize phage-resource development and guide cocktail design for KL-defined CRKP groups.
SN - 1532-2742
ER -