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Published on: January 7, 2019
Data-Driven Engineering of Phages with Tunable Capsule Tropism for Klebsiella pneumoniae
Chao Wang1, Shiwei Wang2, Shisong Jing1,3
1State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
Abstract:
Klebsiella pneumoniae, a major clinical pathogen known for causing severe infections, is attracting heightened attention due to its escalating antibiotic resistance. Phages are emerging as a promising alternative to antibiotics; however, their specificity to particular hosts often restricts their use. In this study, a collection of 114 phages is obtained and subjected to analysis against 238 clinical K. pneumoniae strains, revealing a spectrum of lytic behaviors. A correlation between putative tail protein clusters and lysis patterns leads to the discovery of six receptor-binding protein (RBP) clusters that determine host capsule tropism. Significantly, RBPs with cross-capsular lysis capabilities are identified. The newly-identified RBPs provide a toolbox for customizing phages to target diverse capsular types. Building on the toolbox, the engineered phages with altered RBPs successfully shifted and broadened their host capsule tropism, setting the stage for tunable phage that offer a precise and flexible solution to combat K. pneumoniae infections.
Insights
Bacteriophages (phages) can be engineered to overcome antibiotic resistance in Klebsiella pneumoniae infections. Researchers identified specific phage proteins that control host targeting, enabling customized phages for flexible and precise treatment.
Area of Science:
- Microbiology
- Virology
- Genetics
Background:
- Klebsiella pneumoniae is a significant clinical pathogen causing severe infections.
- Increasing antibiotic resistance in K. pneumoniae necessitates alternative therapeutic strategies.
- Bacteriophages (phages) show promise as antimicrobials but often have limited host specificity.
Purpose of the Study:
- To investigate the host-targeting mechanisms of phages against K. pneumoniae.
- To identify receptor-binding proteins (RBPs) responsible for phage tropism.
- To engineer phages with altered RBPs for broadened host range and customizable therapeutic applications.
Main Methods:
- Screening 114 phages against 238 clinical K. pneumoniae strains to assess lytic activity.
- Analyzing correlations between phage tail protein clusters and observed lysis patterns.
- Identifying and characterizing six distinct RBP clusters determining host capsule tropism.
- Engineering phages by altering RBPs to modify and expand their host range.
Main Results:
- A spectrum of lytic behaviors was observed across the tested phages.
- Six RBP clusters were identified as key determinants of host capsule tropism.
- RBPs exhibiting cross-capsular lysis capabilities were discovered.
- Engineered phages demonstrated successful shifts and broadening of host capsule tropism.
Conclusions:
- Receptor-binding proteins (RBPs) are crucial for phage specificity against K. pneumoniae.
- A toolbox of RBPs allows for the customization of phages to target diverse capsular types.
- Engineered phages with modified RBPs offer a tunable and flexible approach to combat K. pneumoniae infections, addressing antibiotic resistance challenges.
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