The potential of mycobacterial-killing bacteriophages for tuberculosis control, including diagnosis, infection prevention, and treatment, has been proven. However, phage therapy for tuberculosis remains challenging due to the specific nature of the infectious process, primarily because the causative agents of tuberculosis—mycobacteria—live within macrophages and granulomas, making them inaccessible or difficult for bacteriophages to reach. However, in the late stages of the disease, a significant number of mycobacteria can exist outside cells and, therefore, be accessible to phage treatment, as has been demonstrated for Mycobacterium abscessus infection.

A potential advantage of phage-based control of tuberculosis infection is the relatively low variability of clinical strains in their susceptibility to phages. This means that some phages infect a wide range of M. tuberculosis strains. The use of bacteriophages could help shorten the course of antibiotic therapy, provide a new tool in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, and protect new antibiotics from the rapid development of resistance.

Read also: Bacteriophages against mycobacteria, phage therapy for tuberculosis

Scientists from the University of Pittsburgh (USA) created a phage cocktail of five mycobacteriophages with broad specificity against M. tuberculosis strains * . The properties of the bacteriophages in the cocktail were further optimized using genetic and genetic engineering approaches. Specifically, lysogenic phages were converted to lytic ones (by removing a repressor gene), the range of phage specificity was expanded, and the risk of bacterial phage resistance was minimized.

The cocktail effectively killed all tested M. tuberculosis strains except L6, which is not widely distributed and was detected only in a limited area. Several other regional strains of the tuberculosis pathogen were not used in the testing.

The incidence of bacterial resistance to the phage cocktail was low. Furthermore, the cocktail effectively killed M. tuberculosis when used in combination with antibiotics; in particular, bacteriophages demonstrated activity against antibiotic-resistant bacteria.

Phage therapy has repeatedly demonstrated high safety for humans, therefore, according to the authors, it is advisable to conduct clinical trials to determine the scope of application of mycobacteriophage cocktails – in a wide range of patients or only in certain situations.

* Guerrero-Bustamante CA, Dedrick RM, Garlena RA, Russell DA, Hatfull GF. Toward a phage cocktail for tuberculosis: susceptibility and tuberculocidal action of mycobacteriophages against diverse Mycobacterium tuberculosis strains. mBio, 2021; 12:e00973-21. https://doi.org/10.1128/mBio.00973-21 .