It takes months to treat even drug susceptible TB. Even in culture, most TB cells die quickly in the face of drug but some TB bacteria are persistently tolerant of drug. Here we seek to understand why genetically identical TB bacilli are very difficult to eliminate with antibiotics while others are quite susceptible. In addition, we seek to identify genetic mutations that put some TB strains at risk of acquiring drug resistance and thus treatment failure, though they don’t directly confer high-level drug resistance.