FIG 4.

Existing stringent response inhibitors are unable to reverse the tolerance exhibited by a stringent response-activated strain. Wild-type Newman and the F128Y mutant were exposed to either 4× the MIC ciprofloxacin or cefazolin in the presence of different stringent response inhibitors: relacin (1 mM) and ciprofloxacin (A), relacin (2 mM) and cefazolin (B), and DJK-5 (5 μg/ml) and ciprofloxacin (C). Data shown are the means of three replicates; error bars, where visible, represent the SD. Asterisks indicate statistically significant differences between means as determined by an unpaired t test (* and **, P ≤ 0.05 and P ≤ 0.01, respectively; ns, not significant [P > 0.05]). In panel A, no statistically significant differences between with/without inhibitor were detected for either strain at any time point. Dashed gray lines indicate the approximate minimum duration for killing (MDK) 90% of the population (50% in panel B) for each strain. MDK values interpolated from the data shown are given in Table S1 in the supplemental material. Raw data in log₁₀ CFU/ml are shown in Fig. S3.