Increases the Infectivity to Burkholderia pseudomallei
This genetically modified bacteriophage therapy offers diagnostic and treatment applications for Melioidosis, a tropical disease caused by Burkholderia pseudomallei infections. The U.S. Departments of Health and Human Services (HHS) and Agriculture (USDA) identify B. pseudomallei as a tier 1 biothreat due to its high mortality rate of 10-50%3. B. pseudomallei is a highly resilient pathogen with antimicrobial-resistant capabilities, making it a potential bioweapon3. The emergence of antibiotic resistance and the extended treatment duration, up to 20 weeks, pose significant challenges in combatting melioidosis. Available treatment involves prolonged intravenous antibiotics, followed by oral antimicrobial prescriptions for 3-6 months.
Melioidosis, like other bacterial infections, must be identified before treatment begins. Microbial diagnostics are essential to global health, with an estimated market size of USD 3.68 billion in 2023. The diagnostic market is projected to reach USD 11.25 billion in 2033, demonstrating an 11.82% increase. Diagnostic kits and labs are required in all parts of the world to combat this disease.
Researchers at the University of Florida have developed a bacteriophage therapy targeting B. pseudomallei infections. This phage, ?PK23V1, a part of the P2-like myophage group, features a point mutation in the phage tail protein that enhances its ability to infect B. pseudomallei, even with diverse surface receptors present. The mutation increases the phage's infectivity rate, enabling more efficient delivery of antimicrobial agents to the infection site. During the discovery process, researchers designed a phage specificity screening assay to tackle receptor binding diversity, which the P2-like myophage successfully addresses. Consequently, this bacteriophage presents new treatment and diagnostic options for Melioidosis, improving the infectivity rate and offering a viable solution to resilient infections.
Application
This genetically modified bacteriophage (?PK23V1) can be used for B. pseudomallei treatment and diagnostic analysis
Advantages
- Increases binding specificity for treating B. pseudomallei infections, leading to an effective treatment solution
- Can bind to multiple types of receptors even in the absence of O-Antigen and Capsular Polysaccharides, resulting in a highly versatile phage to treat different strains of B. pseudomallei
- Improves receptor binding capabilities of the ?PK23V1 phage, increasing its use for different diagnostic applications to identify agents of infection
Technology
?PK23V1 is a mutant bacteriophage classified as a P2-like myophage belonging to the Peduovirdiae family. A point mutation, N716K, in the phage tail fiber protein (GpH) connects to the bacteriophage’s high level of specificity. The single nucleotide mutation results in cystine substituting adenine. In turn, the missense mutation in the protein converts asparagine (N) to lysine (K). This modification to the phage tail fiber protein expands the host’s binding range even in the absence of capsular polysaccharides and O-antigens, which often contribute to therapeutic delivery issues. In samples, the modified phage infected up to 82.4% (117/142) of the tested B. pseudomallei strains, displaying a remarkable ability to transfer therapeutics. The discovery reveals information about P2 bacteriophage receptor binding capabilities and expands its use for diagnostic purposes, as well.
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