High-throughput, automated approach to phage therapy

Phage therapy has been practiced in some countries for decades, and now it is undergoing Phase 1 clinical trial in the USA. In the face of emerging antibiotic resistance, phage therapies offer promising alternatives to antibiotics, and are predicted to be a better option for precisely killing invading pathogens while leaving resident microbiota intact. Developing phage therapy will require the isolation and characterization of phages specific for particular bacterial targets, and rigorous development and testing of protocols to minimize the potential for resistance. To do this, EpiBiome is creating a high-throughput automated pipeline for phage discovery, which can isolate thousands of phages per day for a single bacterial target. Isolated phages are then further characterized to identify those that are best for therapeutic use. A key characterization step is to determine which host components mutate to confer resistance to each phage. EpiBiome investigates this by isolating bacteriophage insensitive mutants, or ‘BIMS’. Using high-throughput tools to sequence the genomes of many BIMS enables identification of the phage targets and provides information regarding resistance mechanisms. Understanding which host structures confer resistance offers a general understanding of the mechanism of resistance to each phage, which enables EpiBiome to engineer better phage cocktails for treatment. This high-throughput automated approach promises to help revolutionize phage therapy through greatly facilitating phage discovery and improving our understanding of host resistance.