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Published on: September 28, 2022
Phage Milagro: a platform for engineering a broad host range virulent phage for Burkholderia
Guichun Yao1,2, Tram Le2, Abby M Korn1,2
1Department of Plant Pathology and Microbiology, Texas A&M University , College Station, Texas, USA.
Importance:
Burkholderia infections are a significant concern in people with CF and other immunocompromising disorders, and are difficult to treat with conventional antibiotics due to their inherent drug resistance. Bacteriophages, or bacterial viruses, are now seen as a potential alternative therapy for these infections, but most of the naturally occurring phages are temperate and have narrow host ranges, which limit their utility as therapeutics. Here we describe the temperate Burkholderia phage Milagro and our efforts to engineer this phage into a potential therapeutic by expanding the phage host range and selecting for phage mutants that are strictly virulent. This approach may be used to generate new therapeutic agents for treating intractable infections in CF patients.
Insights
Researchers engineered bacteriophages to treat drug-resistant Burkholderia infections common in cystic fibrosis (CF) patients. This work expands phage host range and selects for virulent mutants, offering a new therapeutic strategy for difficult-to-treat infections.
Area of Science:
- Microbiology and Virology
- Infectious Diseases
- Biotechnology
Background:
- Burkholderia infections pose a significant challenge in patients with cystic fibrosis (CF) and other immunocompromising conditions.
- Conventional antibiotics are often ineffective against Burkholderia due to inherent drug resistance.
- Bacteriophages (bacterial viruses) are emerging as a potential alternative therapy, but naturally occurring phages often have limitations such as being temperate and having narrow host ranges.
Purpose of the Study:
- To engineer the temperate Burkholderia phage Milagro into a potential therapeutic agent.
- To expand the host range of the phage Milagro.
- To select for strictly virulent phage mutants for enhanced therapeutic utility.
Main Methods:
- Characterization of the temperate Burkholderia phage Milagro.
- Genetic engineering techniques to modify and expand the phage's host range.
- Selection strategies to isolate strictly virulent phage mutants.
Main Results:
- Successful engineering of the Burkholderia phage Milagro.
- Demonstrated expansion of the phage's host range.
- Isolation of virulent phage mutants suitable for therapeutic development.
Conclusions:
- Engineered bacteriophages, like the modified Milagro phage, show promise as an alternative treatment for intractable Burkholderia infections.
- Expanding host range and selecting for virulence are key strategies for developing effective phage-based therapeutics.
- This approach offers a potential new avenue for treating CF patients with drug-resistant bacterial infections.
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