SBIR Topic 131: Development of Bacteriophage for Treatment of Mycobacterial Infections

Tuberculosis (TB) is a leading cause of death due to infectious diseases, with an estimated 10 million people failing ill with it each year. A quarter of world's population is estimated to be infected with Mycobacterium tuberculosis, the causative agent of TB. Compared to TB, Non-tuberculosis mycobacteria (NTM) have lower virulence but are known to cause infections of the lungs, skin, soft tissues, bursae, joints, tendon sheaths, and bones, in immunocompromised individuals. New therapies to tackle TB and NTM infections are critically needed. Mycobacteriophages that target mycobacterial infections have been isolated and successfully utilized in compassionate use trials. However, majority of the phage screening research has not included mycobacterial biofilms which are known to play a critical role in pathogenicity of infections. The proposed research effort will develop robust microfluidic mycobacteria models that will support pre-clinical research in mycobacteriophage therapy. Phase I research will establish proof-of-concept by establishing biofilms of multiple mycobacteria species and studying phage infections using high-resolution confocal microscopy and impedance measurements. Developed biofilm models will be tested against nebulized phage therapy, antibiotic and phage co-administration, and for studying polymicrobial films. Phase II research will advance the models to a diverse panel of mycobacteria strains including clinical isolates.