The First Step To Bacteriophage Therapy: How To Choose The Correct Phage

Bacteriophages are viruses that can kill bacteria but are harmless to eukaryotic cells. In natural environments they have a dominant role in controlling bacterial populations. Thus, in the era of the emergence and spread of multidrug resistant bacterial pathogens they are more and more often seen as promising antibacterial agents that could be an alternative to antibiotics. Bacteriophages' main advantages as therapeutics are their ability to target bacteria of certain strains or species, without any harmful effect on the rest of the bacterial microflora, as well as their self-limiting propagation which is controlled by the availability of a sensitive host. Moreover, bacterial antibiotic resistance is not a barrier for phage infection. Only a limited number of phages from environmental isolates meet the criteria that are expected for therapeutic phages. Here we describe the most important of these criteria and provide a guide for selecting potential therapeutic phages for further studies in animal models. The ability of many phages to remain in a bacterium in the form of a prophage and increase its adaptive potential, as well as to participate in the horizontal gene transfer between bacterial cells, a priori precludes their use in therapy due to safety concerns. Factors that matter in the prediction of the remaining phages' therapeutic efficacy include host range and killing potential, adsorption kinetics and propagation efficiency, stability during storage and under 'natural conditions', the ability to penetrate encapsulated cells or biofilms, easiness of purification. The choice or modification of phage propagation host, which cannot be a source of contaminating phages, plasmids and toxins, appears nearly as important as the selection of a proper therapeutic phage.