Growth conditions and rifampin susceptibility

The susceptibility of Escherichia coli to rifampin was measured during unlimited growth in rich and poor media and during chemostat growth limited by the carbon source. During batch growth at low turbidities, the susceptibility of the bacteria increased as the growth rate decreased, consistent with the longer time available for drug penetration in the poorer media. During chemostat culture, the bacteria remained highly susceptible or became genetically resistant, dependent on the manner in which the bacteria were exposed to the antibiotic. If the concentration of rifampin was abruptly raised, susceptible cells were replaced by genetically resistant cells. However, if the concentration of antibiotic was raised slowly, the genetically susceptible cells continued to grow. This difference in response of chemostat cultures according to mode of drug administration was attributed to an inducible detoxification of the drug by the bacteria, because the susceptible genotype is maintained only when the concentration of rifampin is increased gradually and when a high population of cells is maintained. Direct evidence for the inactivation of the rifampin from the bioassay of culture supernatants is presented.