Figure 5.

Tolerance and persisters. Tolerance is defined as the ability of drug-susceptible bacteria to survive for an extended period antimicrobial concentrations that would normally kill them (i.e. MIC_WT). Tolerance is hypothesized to be responsible for the long treatment regimens required to achieve sterility in MTBC infections. Persistence may be defined as ‘heterotolerance,’ when only a subset of the population exhibits the tolerance phenotype. Bacterial cells that exhibit the tolerance phenotype are known as ‘persisters,’ and the granuloma caseum likely harbors large populations of non-replicating MTBC persisters. In between treatment doses, antimicrobial concentrations may drop below MIC_WT. Persisters may revert back to a replicating phenotype during this period and lead to population regrowth.