Catalase deficiency sensitizes multidrug-resistant Mycobacterium tuberculosis to the ATP synthase inhibitor bedaquiline

Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to the first-line drugs isoniazid and rifampin, is a growing source of global mortality and threatens global control of tuberculosis disease. The diarylquinoline bedaquiline has recently emerged as a highly efficacious drug against MDR-TB and kills Mycobacterium tuberculosis cells by inhibiting ATP synthase activity. However, mechanisms underlying bedaquiline's potentiated efficacy against MDR-TB remain unknown. Here we investigate bedaquiline hyper-susceptibility in isoniazid-resistant Mycobacterium tuberculosis using systems biology approaches.