This technology has applications in antibacterial therapies.
Overcoming the development of antibiotic resistance in pathogenic bacteria poses a tremendous medical challenge. Whereas small molecule drugs have been the standard antibiotic for several decades, bacteriophages, or viruses that infect bacteria, could prove to be a viable alternative. One significant challenge of bacteriophage-based therapy, is the specificity of each virus; thus, simultaneously targeting multiple bacteria in an infection would require a cocktail of viruses, complicating both development of therapies and increasing the associated regulatory hurdles. One solution would be to engineer a single bacteriophage to target multiple hosts; however, current techniques for bacteriophage engineering are low in efficiency and throughput.
Researchers at MIT have developed a new method for addressing the challenges faced in engineering bacteriophage host ranges. First, mutations are inserted into the tail region of phage DNA with PCR. A library of mutated phage fragments is then transformed along with a yeast artificial chromosome (YAC) into a population of yeast, where homologous recombination between the phage fragments and the YAC can occur. The resulting population of phage is extracted from the yeast, and then transfected into a bacterial colony, and tested for host range specificity. Using this method allows for systematically generating and selecting phage variants with desired functionality.
- Systematically modify bacteriophage genome for wider range of specificities
- Allows for modifying bacteriophage in non-bacterial host
Efficient and versatile method