FIG. 8.
(A) Preexisting drug-tolerant cells are not multidrug tolerant. The bactericidal activities of frontline drugs were evaluated against logarithmically growing cultures of M. tuberculosis either alone or in combination for either 4 days (open bars) or 7 days (filled bars). The drugs used in the experiment were isoniazid (H), rifampin (R), and pyrazinamide (Z) at 1, 4, and 200 μg/ml, respectively. Percent survival was measured as the number of CFU/ml in the culture after incubation with the drug relative to the number of CFU/ml in the culture pretreatment. The results shown are from one of three independent experiments. (B) Persisters in E. coli are multiply drug tolerant. Early-log-phase cultures of E. coli were exposed to a single drug for 3 h. After 3 h of exposure, a second drug was added for an additional 3 h. The drugs used in this experiment were levofloxacin (L), streptomycin (S), and ampicillin (A) at concentrations of 10 μg/ml, 24 μg/ml, and 100 μg/ml, respectively. Following drug exposures, the surviving bacilli were harvested by centrifugation and washed, and bacterial counts were determined by plating on agar medium.