Functional genomics of Mycobacterium tuberculosis
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, an infectious disease of the lungs that kills over a million individuals a year worldwide and is estimated to latently infect ⅓ of the human population. Antibiotic resistance among Mtb isolates is increasing and the BCG vaccine does not provide complete protection against disease, therefore tuberculosis is likely to remain a global health threat for years to come. We want to understand how genetic diversity in clinical isolates of Mtb impacts the ability of a strain to develop antibiotic resistance or escape the protection conferred by vaccination. To answer these questions, we use functional genomics (Carey et al. 2018), and high-throughput phenotyping in vitro and in mouse models (Carey et al. 2022).
Non-tuberculous mycobacteria
Non-tuberculous mycobacteria (NTM) are a group of related environmental bacteria that can be opportunist pathogens in individuals with compromised immune systems or underlying lung disease. NTM infections are notoriously difficult treat due to their intrinsic resistance to many antibiotics, requiring months to years of multi-drug therapy. Infections from NTM are increasing in prevalence. What makes some strains of these environmental bacteria virulent and able to establish infections in humans remains unclear. The basis of their inherent antibiotic resistance also remains incompletely understood. We are investigating these questions with forward genetics, comparative genomics across large panels of patient isolates, and infection models. We are currently focused on two NTM species, Mycobacterium avium, the most common cause of pulmonary NTM infections, and Mycobacterium abscessus, which has emerged as an antibiotic treatment ‘nightmare’ due to its intrinsic resistance to so many antimicrobials.