Using rpoS, tolC, ompF, and recA knockouts, we investigated their effect on the physiological response and lethality of cipro oxacin in E. coli growing at different rates on glucose, succinate or acetate. We have shown that, regardless of the strain, the degree of changes in respiration, membrane potential, NAD/NADH ratio, ATP and glutathione (GSH) strongly depends on the initial growth rate and the degree of its inhibition. The deletion of the regulator of the general stress response RpoS, although it in uenced the expression of antioxidant genes, did not signi cantly affect the tolerance to cipro oxacin at all growth rates. The mutant lacking TolC, which is a component of many E. coli e ux pumps, showed the same sensitivity to cipro oxacin as the parent. The absence of porin OmpF slowed down the entry of cipro oxacin into cells, prolonged growth and shifted the optimal bactericidal concentration towards higher values. De ciency of RecA, a regulator of the SOS response, dramatically altered the late phase of the SOS response (SOS-dependent cell death), preventing respiratory inhibition and a drop in membrane potential. The recA mutation inverted GSH uxes across the membrane and abolished cipro oxacininduced H 2 S production. At all growth rates, this mutation reduced logCFU ml -1 by about 3 orders of magnitude. All studied mutants showed an inverse linear relationship between logCFU ml -1 and the speci c growth rate, that is, the activity of antibiotic targets. Mutations shifted the plot of this dependence relative to the parental strain according to their signi cance for cipro oxacin tolerance.