Directed Evolution Enhanced Phage Therapy.
Phage therapy has long been available for numerous antibiotic applications. However, the practice was largely replaced for the more cost effective, widespread use of conventional antibiotic compounds. In light of the growing number of antibiotic resistant pathogens encountered in the clinic, novel therapeutic avenues to extinguish resistant or recalcitrant organisms are desperately needed.
A critical barrier limiting the effectiveness of current phage therapies is the lack of phage propagation in the treatment environment (such as the wound). This is largely due to vast differences in the abiotic milieu of the treatment environment and the conditions from which the phage was isolated.
Using directed evolution techniques, the inventor herein claims to reduce this ineffectiveness by creating mutant bacteriophage with the ability to propagate dramatically in the presence of a concentrated sugar solution (applied with the phage during treatment).
This regimen allows for 1) an environment for optimal phage replication and 2) an environment not optimal for bacterial replication due to osmotic constraints (in a sense, bacteriostatic). These simultaneously provide a primed “breeding ground” for phage replication within bacterial hosts that, due to reduced bacterial proliferative capacity, will mitigate phage resistance.