FIG 1 .

INH-sensitive survivors of INH treatment induce a transcriptional program consistent with a slow-growing stress-resistant state. (a) Treatment of M. tuberculosis with INH kills >99% cells in 4 days, leaving a largely INH-sensitive population from which an INH-resistant population emerges. (b) Survivors of 4 days of INH treatment induce genes consistent with INH sensitivity; the persister stimulon includes a subset of the enduring hypoxic response (EHR). Persister stimulon is defined here narrowly as genes statistically significantly induced >twofold at a false discovery rate (FDR) of <0.4% by SAM. EHR and INH stimulons were similarly defined by Rustad et al. (21) and Fu (18). (c) Heat maps of the persister stimulon in biological triplicates mapped onto genes induced by 4-h INH treatment, stress-responsive genes, genes involved in growth and cell division, the ATP synthase, the type I NADH dehydrogenase, and the dosR regulon. The scale indicates ±3-log₂-fold changes relative to expression at day 0.