Fig. 1

The viability of M. tuberculosis H37Rv at either a fast growth rate or a slow growth rate in response to PZA exposure. Viability of Mycobacterium tuberculosis H37Rv growing at either a slow growth rate (69.3 h mean generation time (MGT); Panel a or a fast growth rate (23.1 h MGT; Panel b The cultures were exposed to sequential increases in the concentration of PZA in a step-wise manner every 2 MGTs and bacterial survival was measured. The levels of PZA used were 25, 50, 100, 250 and 500 μgml⁻¹; these concentrations are indicated on each graph between the vertical dotted lines to show each exposure period. Each growth rate was cultured in duplicate (solid and dashed black lines). The washout rate of the culture system is represented by the gradient of the dashed red lines. A reduction in bacterial number (cfuml⁻¹) that followed this rate was indicative of a bacteriostatic drug effect. A more rapid rate of loss of viable cells indicated a bactericidal effect, and a less rapid rate indicates a sub-inhibitory effect. The limit of detection (LOD; defined as the level calculated from the presence of a single colony in one technical replicate) is indicated by the line labelled LOD. The time-points for which transcriptional analyses were performed are indicated as follows: i) pre-PZA phase, ii) bacteriostatic phase (4 h after the addition of 25 μgml⁻¹) iii) early recovery phase (4 h after the addition of 100 μgml⁻¹ PZA) and iv) late recovery phase (2 MGT after the addition of 100 μgml⁻¹ PZA)