A Novel Bacteriophage-Antibiotic Synergy for the Effective Treatment of Tuberculosis

Mycobacterium tuberculosis, one of the most lethal infections in the world, causes nearly two million deaths per year and remains a highly problematic therapeutic target due to its increasing antibiotic resistance. However, bacteriophages, or viruses that specialize in lysing bacteria, could potentially treat any type of bacterial infection. Because cross-resistance is difficult to acquire, it was proposed that the synergy of antibiotic and bacteriophage would provide for greater efficiency than that of either agent alone for the treatment of a model organism for tuberculosis over time. After minimum inhibitory concentrations (MICs) were calculated using a broth dilution method, increasing multiples of the MICs (0.25x, 0.50x, and 0.75x MIC) for isoniazid and ethambutol, tested independently, were diluted with rising PFUs/mL (10¹, 10², and 10⁴ PFUs/mL) of mycobacteriophage D29 and compared to the effects of mycobacteriophage D29 and antibiotic alone on bacteria over time. Samples were taken every 4.5 hour intervals for nearly 24 hours using optical density (OD) at 600 nm; samples were also plated before and after for visualization of the effects of each treatment. Results indicate that different antibiotics, due to distinct mechanisms of action, affect synergy efficiency, which has not been demonstrated in studies before. The hypothesis was supported. It was also found that the mycobacteriophage D29-ethambutol synergy was the significantly more effective than all other treatments. All tested mycobacteriophage D29-ethambutol synergies completely treated the bacteria within 18 hours and treated with >20-40% greater efficiency than antibiotics alone. These findings indicate that the novel synergy of ethambutol and bacteriophage is a significantly more effective and efficient alternative to the current methods of treatment. Thus, bacteriophage-antibiotic synergies have enormous potential for improving the treatment of tuberculosis and other infections.