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Updated: Jan 20, 2026
A Phage Therapy against Pseudomonas aeruginosa Infection in Zebrafish Embryos
High murine blood persistence of phage T3 and suggested strategy for phage therapy
Philip Serwer1, Elena T Wright2, John C Lee2
1Department of Biochemistry and Structural Biology, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA. serwer@uthscsa.edu.
Objective:
Our immediate objective is to determine whether infectivity of lytic podophage T3 has a relatively high persistence in the blood of a mouse, as suggested by previous data. Secondarily, we determine whether the T3 surface has changed during this mouse passage. The surface is characterized by native agarose gel electrophoresis (AGE). Beyond our current data, the long-term objective is optimization of phages chosen for therapy of all bacteremias and associated sepsis.
Results:
We find that the persistence of T3 in mouse blood is higher by over an order of magnitude than the previously reported persistence of (1) lysogenic phages lambda and P22, and (2) lytic phage T7, a T3 relative. We explain these differences via the lysogenic character of lambda and P22, and the physical properties of T7. For the future, we propose testing a new, AGE-based strategy for rapidly screening for high-persistence, lytic, environmental podophages that have phage therapy-promoting physical properties.
Insights
Lytic podophage T3 exhibits significantly higher persistence in mouse blood compared to other phages. This finding supports phage therapy development for bacterial infections and sepsis.
Area of Science:
- Microbiology
- Virology
- Immunology
Background:
- Bacteriophage therapy is a promising alternative to antibiotics for treating bacterial infections.
- Understanding phage persistence in vivo is crucial for optimizing therapeutic efficacy.
- Previous studies suggested variable persistence of different phage types in host environments.
Purpose of the Study:
- To determine the persistence of lytic podophage T3 in mouse blood.
- To investigate potential changes in the T3 phage surface during mouse passage.
- To lay the groundwork for optimizing phage selection for bacteremia and sepsis treatment.
Main Methods:
- In vivo studies to assess phage T3 persistence in mouse blood.
- Native agarose gel electrophoresis (AGE) to characterize phage surface properties.
- Comparative analysis with previously reported data for other phages (lambda, P22, T7).
Main Results:
- Podophage T3 demonstrated over an order of magnitude higher persistence in mouse blood than lysogenic phages lambda and P22, and lytic phage T7.
- Differences in persistence were attributed to the lysogenic nature of lambda/P22 and the physical properties of T7.
- No significant changes in the T3 surface were reported during mouse passage.
Conclusions:
- Lytic podophage T3 exhibits superior persistence in mouse blood, suggesting its potential for phage therapy.
- The study highlights the importance of phage characteristics (lytic vs. lysogenic, physical properties) in determining in vivo persistence.
- A novel AGE-based screening strategy is proposed for identifying high-persistence, therapeutic-grade podophages.
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