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Engineering a T7 bacteriophage to attenuate LPS-driven inflammatory responses during bacteriolysis.
Tong Yu1, Junjiao Pang1, Mengge Chen1
1School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China.
Applied and Environmental Microbiology
|May 4, 2026
Summary
Engineered bacteriophages combat Gram-negative infections by killing bacteria and reducing inflammation. T7-nluc monitors infections in real-time, while T7-phoa releases alkaline phosphatase to neutralize harmful lipopolysaccharides (LPS).
Area of Science:
- Microbiology
- Biotechnology
- Immunology
Background:
- Bacterial lysis during Gram-negative infection treatment releases lipopolysaccharide (LPS), potentially worsening inflammation.
- Bacteriophage therapy offers a promising alternative for drug-resistant Gram-negative infections but faces challenges related to LPS release.
Purpose of the Study:
- To engineer bacteriophages for simultaneous bacterial killing and modulation of LPS-induced inflammation.
- To develop a NanoLuc reporter bacteriophage (T7-nluc) for real-time infection monitoring.
- To create a therapeutic bacteriophage (T7-phoa) releasing alkaline phosphatase (PhoA) to neutralize LPS bioactivity.
Main Methods:
- Engineering of T7 bacteriophages for reporter (T7-nluc) and therapeutic (T7-phoa) functions.
- In vitro characterization of bacteriophage lytic activity, bioluminescence, and PhoA release.
- In vivo evaluation in Galleria mellonella and Danio rerio infection models.
Main Results:
- Both engineered bacteriophages exhibited lytic activity comparable to wild-type T7.
- T7-nluc enabled dynamic, low-background monitoring of bacterial burden in vivo.
- T7-phoa treatment improved survival, reduced inflammation, and accelerated resolution in infection models without compromising bacterial clearance.
Conclusions:
- A modular bacteriophage engineering strategy can combine bacterial killing with real-time infection monitoring.
- T7-phoa effectively reduces LPS bioactivity and associated inflammation at the infection site.
- This approach holds potential for enhancing bacteriophage-based treatments for Gram-negative infections.
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