Mycobacterium tuberculosis (Mtb) is the leading cause of death due to infectious disease. By investigating the mechanisms that enable this bacterium to cause tuberculosis (TB) and evade antibiotics, the Rock lab aims to lay the foundation for new therapeutic strategies to improve control of this epidemic.
Host-pathogen interactions. A defining feature of Mtb’s pathogenicity is its ability to chronically infect an immune competent host for years, if not a lifetime. The physiological adaptations that enable Mtb to persist in the face of a robust immune response and sustain chronic infection also render the bacterium tolerant to antibiotics. While long recognized as a singularly important aspect of Mtb’s lifecycle, the mechanisms mediating chronic Mtb infection remain largely unknown. The Rock lab is developing new functional genomic approaches to define the basis for chronic Mtb infection.
Bug-drug interactions. TB can be treated with antibiotics. However, TB treatment requires a combination of four drugs taken for 4-6 months. This lengthy treatment regimen is one of the most important roadblocks to effective TB control. Why is TB so difficult to treat? While the answer is multifactorial, one major difficulty is the resistance of the infecting bacterium– both intrinsic and acquired– to many distinct classes of antimicrobials. Beyond resistance, antibiotic tolerant bacteria arise during infection, further complicating treatment. The Rock lab investigates the molecular mechanisms of antibiotic tolerance and resistance in Mtb.
NTMs. Non-tuberculous mycobacteria (NTM) like M. abscessus and M. avium are increasingly problematic pathogens. These bacteria cause skin and soft tissue infections and are a common opportunistic pathogen of the lung in patients with underlying pulmonary dysfunction, including cystic fibrosis. NTM infections can be exceedingly difficult to treat. The Rock lab leverages chemical-genomic approaches to understand mechanisms of antibiotic resistance in NTMs, knowledge which can then be used to facilitate development of new drugs to treat these infections.