A Klebsiella-phage cocktail to broaden the host range and delay bacteriophage resistance both in vitro and in vivo

Huanchang Chen; Haifeng Liu; Yanchun Gong; Rhys A Dunstan; Zhexiao Ma; Cui Zhou; Deyi Zhao; Miran Tang; Trevor Lithgow; Tieli Zhou

doi:10.1038/s41522-024-00603-8

A Klebsiella-phage cocktail to broaden the host range and delay bacteriophage resistance both in vitro and in vivo

NPJ Biofilms Microbiomes. 2024 Nov 14;10(1):127. doi: 10.1038/s41522-024-00603-8.

Authors

Huanchang Chen^{1

2}, Haifeng Liu¹, Yanchun Gong¹, Rhys A Dunstan^{2

3}, Zhexiao Ma⁴, Cui Zhou¹, Deyi Zhao⁴, Miran Tang¹, Trevor Lithgow^{5

6}, Tieli Zhou⁷

Affiliations

¹ Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang, China.
² Centre to Impact AMR, Monash University, Melbourne, VIC, 3800, Australia.
³ Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia.
⁴ School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁵ Centre to Impact AMR, Monash University, Melbourne, VIC, 3800, Australia. [email protected].
⁶ Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia. [email protected].
⁷ Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang, China. [email protected].

PMID: 39543151
DOI: 10.1038/s41522-024-00603-8

Abstract

Bacteriophages (phages), viruses capable of infecting and lysing bacteria, are a promising alternative for treating infections from hypervirulent, antibiotic-resistant pathogens like Klebsiella pneumoniae, though narrow host range and phage resistance remain challenges. In this study, the hypervirulent K. pneumoniae NTUH-K2044 was used to purify phage ΦK2044, while two ΦK2044-resistant strains were used to purify two further phages: ΦKR1, and ΦKR8 from hospital sewage. A detailed characterization showed that ΦK2044 specifically killed KL1 capsule-type K. pneumoniae, while ΦKR1 and ΦKR8 targeted 13 different capsular serotypes. The phage cocktail (ΦK2044 + ΦKR1 + ΦKR8) effectively killed K. pneumoniae in biofilms, pre-treatment biofilm formation, and delayed phage-resistance. The phage cocktail improved 7-day survival in Galleria mellonella and mouse models and showed therapeutic potential in a catheter biofilm model. In summary, this proof-of-principle phage cocktail has a broad host range, including hypervirulent and highly drug-resistant K. pneumoniae, and serves as a promising starting point for optimizing phage therapy.

Grants and funding

82472338/National Natural Science Foundation of China (National Science Foundation of China)