The primary focus of the Karakousis Lab is to understand the molecular basis of persistence and reactivation in Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). Major research activities include studying the adaptation of M. tuberculosis to stress conditions believed to be important in the infected human host, as well as the phenomenon of phenotypic tolerance to antibiotics. In particular, the regulatory cascade involved in the mycobacterial stringent response is under active investigation. A systems biology-based approach is being used to identify host defense mechanisms responsible for immunological control of M. tuberculosis growth, as well as M. tuberculosis regulatory and metabolic pathways required for bacterial persistence and antibiotic tolerance.
The laboratory is also actively investigating the repurposing of various clinically available agents with immune-modulatory properties as adjunctive host-directed therapy, in order to shorten the duration of TB treatment and improve lung pathology. A randomized clinical trial of Statins as Adjunctive Therapy for TB (StAT-TB trial) is investigating the potential adjunctive role of pravastatin in improving microbiological and lung-function outcomes in HIV-infected and uninfected individuals with drug-susceptible, pulmonary TB in South Africa. Finally, molecular assays using blood, sputum, and urine samples are being investigated with the goal of developing rapid, sensitive, and specific point-of-care tests for TB diagnosis and detection of drug resistance.