|Microgen is a major Russian pharmaceutical company that|
produces many different phage therapies. Source
former Soviet Union), their composition, safety, and efficacy have not been scientifically evaluated . If we are to move forward in our endeavors toward using phages
therapeutically, we must address this lack of knowledge by evaluating the composition, efficacy, and safety of phage cocktails which have long been used in Russia.
To provide insight into Russian phage cocktails that are currently in use, McCallin et al evaluated the composition and efficacy of a Microgen phage therapy cocktail which is marketed for use in E. coli and proteus bacteria infections. The group first assessed the composition of the therapeutic phage cocktails by purifying the phage DNA and performing high-throughput, shotgun sequencing for metagenomic analysis (this means that they obtained an incredibly large number of random DNA sequences from the isolated phage genomic DNA, and were able to use the sequences to determine what phages are present and what genes they contain). The group found that the cocktail was composed of 18 phage types which had high similarities to known E. coli phages, as well as potential proteus phages. These finding were also supported by their electron microscopy findings.
Not only did McCallin et al use their phage metagenome to determine the therapeutic phage cocktail composition, they also screened the phage DNA for potentially dangerous genes including virulence factor genes that could be transmitted from the phages to the patient's resident bacteria. One aspect of potential virulence that the authors did not really go in to was the presence of potential temperate phages present in the phage cocktail. Temperate phages are often capable of integrating their DNA into their host bacteria, persist as latent infections until the bacteria becomes stressed, and significantly transfer genes between bacteria, including potential virulence factor genes. I think that the presence of temperate phages in phage therapy cocktails could present a safety concern because its administration to patients may promote gene transfer among bacteria. As far as I know, there is no literature investigating this concern, so this may become an important point to address as we move forward with development of phage therapies. If temperate phages in phage therapies do in fact present a safety issue, it will be important for quality control methods to include screenings for temperate phages as the therapeutic cocktails are produced.
|Electron microscopy images of phages contained in the|
Microgen phage therapy cocktail. Reference 
This study is important because it offers us some initial insight into the composition of existing phage therapy cocktails in an area that has been using this technology for a long time. This will serve as an important reference for future studies which may use this cocktail, or studies which may compare different phage compositions to different safety or efficacy outcomes. I also think the suggestion of safety in their human cohort will support further research evaluating the use of phage therapy as a medicine under FDA and EMA approval. Overall this is an interesting report which provides valuable insight into an important therapy which has been understudied over past decades.