Mycobacterium tuberculosis is a bacterial pathogen and one of the leading causes of death due to infectious disease. In 2020, an estimated 10 million people fell ill with tuberculosis (TB) worldwide. By investigating the mechanisms that enable this bacterium to cause TB and evade antibiotics, the Rock lab aims to lay the foundation for new therapeutic strategies to improve control of this pandemic.
Most people infected with Mtb do not become ill. However, in 5-10% of immune competent individuals, the immune system fails to control Mtb and the person develops disease. The mechanisms that enable the pathogen to defeat and persist in the face of a robust adaptive immune response are incompletely understood. The Rock lab is using new genome-scale approaches to define the genetic basis for persistent Mtb infection.
Mtb infection can be treated with antibiotics. However, effective TB treatment requires a combination of four drugs taken for a minimum of six months. This lengthy treatment regimen, thought to be necessitated at least in part by the presence of antibiotic-tolerant bacilli that arise during infection, is one of the most important roadblocks to effective TB control. Worse still, tolerant bacteria can survive and give rise to drug resistant bacteria, thereby fueling the growing problem of drug-resistant TB. The Rock lab investigates the molecular mechanisms of antibiotic tolerance, as well as the mechanisms by which the bacterium can ultimately evolve antibiotic resistance.
Lastly, non-tuberculous mycobacteria (NTM) like M. abscessus and M. avium cause skin and soft tissue infections and are a common opportunistic pathogen of the lung in patients with underlying pulmonary dysfunction, including cystic fibrosis (CF). NTM infections can be exceedingly difficult to treat. The Rock lab leverages genome-scale genetic 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.