Phage-antibiotic synergy suppresses resistance emergence of <i>Klebsiella pneumoniae</i> by altering the evolutionary fitness
Phage-antibiotic synergy (PAS) has been recently proposed as a superior strategy for the treatment of multidrug-resistant pathogens to effectively reduce bacterial load and slow down both phage and antibiotic resistance. However, the underlying mechanisms of resistance suppression by PAS have been poorly and rarely been studied. In this study, we tried to understand how PAS suppresses the emergence of resistance using a hypervirulent <i>Klebsiella pneumoniae</i> (KP) strain and a novel phage H5 in combination with ceftazidime (CAZ) as a model. Our study reveals a novel mechanism by which PAS drives altered evolutionary trajectory of bacterial populations, leading to suppressed emergence of resistance. The findings advance our understanding of how PAS suppresses the emergence of resistance, and are imperative for optimizing the efficacy of phage-antibiotic therapy to further improve clinical outcomes.
Authors
- Kunhao Qin (ORCID: https://orcid.org/0000-0002-3740-4661)
- Jinquan Liu
- Xing Shi (ORCID: https://orcid.org/0000-0003-2778-5373)
- Kai Yang (ORCID: https://orcid.org/0000-0002-3554-3334)
- Kai Zhou (ORCID: https://orcid.org/0000-0002-7320-291X)
- Senxiong Chen
- Tingting Xu (ORCID: https://orcid.org/0000-0002-2913-2133)
- Zheng Liu (ORCID: https://orcid.org/0000-0002-3538-9349)
- Rongchang Chen (ORCID: https://orcid.org/0000-0001-7642-3921)
- Wangrong Wen
- Qiuqing Xu
- Cui Li (ORCID: https://orcid.org/0000-0002-0708-8899)
- Fuxing Wang
Institutions
- Jinggangshan University (CN)
- Jinan University (CN)
- Shenzhen University (CN)
- Chinese Academy of Sciences (CN)
- Southern University of Science and Technology (CN)
- The First People's Hospital of Shunde (CN)
- Chinese University of Hong Kong, Shenzhen (CN)
- Institute of Urban Environment (CN)
- First Affiliated Hospital of Jinan University (CN)
- The Affiliated Shunde Hospital of Jinan University
Publication Details
- Journal
- mBio
- Published
- 2024-09-09
- DOI
- https://doi.org/10.1128/mbio.01393-24
- Citations
- 27
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 12.39
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- National Key Research and Development Program of China
- Basic and Applied Basic Research Foundation of Guangdong Province