Inactivating conditions of therapeutic mycobacteriophages

There is a need for new therapies to treat drug-resistant nontuberculous
mycobacteria (NTM) disease. Bacteriophages (phages), which are viruses
that infect and kill bacteria, are actively being explored as an
alternative approach for treating mycobacterial diseases. Several
compassionate-use cases of phage therapy for drug-resistant NTM infections
exhibit favorable outcomes. To further the development of phage therapy,
it is important to recognize and avoid conditions that negatively impact
phage activity during phage production, storage, formulation, or
treatment. Conversely, there is a need to inactivate free phages in
certain preclinical phage therapy experiments. In this study, we
investigated three mycobacteriophages, BPsΔ33HTH-HRM10, Muddy, and
ZoeJΔ4,5 from compassionate-use NTM treatment cases for their sensitivity
to a variety of conditions that included temperature, acid pH, detergents,
mucus, and phage inactivating buffers. Several conditions resulted in
dramatic and rapid reductions in the level of active phage, while others
had no effect. We also observed different sensitivities between the
phages. The results provide valuable information to support further
investigation and development of these phages as therapeutics.