Restoring logic and data to phage-cures for infectious disease

Abstract

Antibiotic therapy for infectious disease is being compromised by emergence of multi-drug-resistant bacterial strains, often called superbugs. A response is to use a cocktail of several bacteria-infecting viruses (bacteriophages or phages) to supplement antibiotic therapy. Use of such cocktails is called phage therapy, which has the advantage of response to bacterial resistance that is rapid and not exhaustible. A procedure of well-established success is to make cocktails from stockpiles of stored environmental phages. New phages are added to stockpiles when phage therapy becomes thwarted. The scientific subtext includes optimizing the following aspects: (1) procedure for rapidly detecting, purifying, storing and characterizing phages for optimization of phage cocktails, (2) use of directed evolution in the presence of bacteriostatic compounds to obtain phages that can be most efficiently used for therapy in the presence of these compounds, (3) phage genome sequencing technology and informatics to improve the characterization of phages, and (4) database technology to make optimal use of all relevant information and to rapidly retrieve phages for cocktails that will vary with the infection(s) involved. The use of phage stockpiles has an established record, including a recent major human-therapy success by the US Navy. However, I conclude that most research is not along this track and, therefore, is not likely to lead to real world success. I find that a strong case exists for action to rectify this situation.

Keywords: phage characterization; phage propagation; phage stockpile; superbug.