Published: ɛ2-phages are naturally bred and vastly superior to wild-type
PhagoMed published details on its phage program PM-399 including a detailed introduction to its proprietary ɛ2-(evolution squared)-phages. ɛ2-phages are a new type of naturally bred S. aureus phages, which are vastly superior to the wild type ancestors, and which are candidates for fighting antibiotic-resistant or biofilm-related infections.
Wild-type phages are often unreliable. They tend to allow quick resistance formation or only reduce bacterial growth rather than eradicating the bacteria. Therefore, genetic engineering is sometimes used to improve the properties of wild-type phages, for example by altering the receptor-binding protein or by introducing various payloads with CRISPR. However, these methods rely on understanding the genes that are modified and for phages the function of 50-80% of genes is completely unknown. PhagoMed therefore searched for a pathway to overcome this limitation in phage engineering.
PhagoMed developed a new phage evolution method, which relies on naturally induced, random changes in the phage genomes, followed by selection for desired properties. Details on this process and the results have just been published in the journal Pharmaceuticals.
The article describes how ɛ2-phages have a vastly improved host range (the capability of lysing many strains within a bacterial species), increased virulence (the property allowing the phages to kill a population of bacteria even at a low starting phage concentration) and reduced resistance formation. The best and most complementary ɛ2-phages were compiled into a phage cocktail, PM-399, which reliably lyses more than 90% of S. aureus strains, independently of their antibiotic resistance status.
Based on the genetic recombination that were found in the ɛ2-phages, PhagoMed also filed two patent applications with a very innovative claim structure, which would not have been possible for wild type phages.
As shown in the publication, ɛ2-phages have increased therapeutic potential via the increased virulence and, due to the increased kinetic host range, also reduce the number of phages required in a fixed cocktail or in a phage bank for personalized phage therapy. Overall, the ɛ2-phages and the cocktail PM-399 are promising candidates for an alternative treatment of S. aureus infections.
The full publication on S. aureus ɛ2-phages can be found here.