Translational Tools for Diagnostics and In Vivo Drug Testing of Non-Tuberculous Mycobacteria (NTM)

Hilton St. Petersburg Bayfront, Florida

Non-tuberculous mycobacteria (NTM) are group of ubiquitous, environmental bacteria that includes several opportunistic pathogens including M. abscessus and M. avium. In the United States, infections due to NTM are more common than the notorious pulmonary pathogen M.tuberculosis (Mtb). NTM pulmonary infections are most common in patients with underlying co-morbidities that impair lung function (i.e. cystic fibrosis) or cause immunosuppression (i.e. HIV). In this project, we have addressed two reasons behind the lack of effective treatments for NTM infections – lack of adequate diagnostics and lack of animal models for in vivo drug testing. First, effective treatment of NTM infections requires species-specific identification of NTM due to differences in drug susceptibility. However, current methods require isolation by culture followed by sequencing. We have developed a diagnostic tool which combines PCR amplification of 16S rRNA followed by highly specific and sensitive differentiation of species using binary deoxyribozyme (BiDz) sensors. Our successful identification of 38 NTM clinical isolates using our panel of BiDz sensors for six clinically relevant NTM species and M.tb validates this rapid and inexpensive tool for identification of NTM. Secondly, to address the lack of appropriateanimal models to study NTM disease and therapeutics, we are developing a novel pulmonary NTM animal model using an immunocompromisedmouse line. Preliminary data suggest this model develops a sustained infection. These novel translational tools for NTM are predicted to facilitate significant improvements in the detection and treatment of NTM infections.