Koch A L, Gross G H
Antimicrob Agents Chemother. 1979 Feb;15(2):220-8. doi: 10.1128/AAC.15.2.220.
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.
在富含营养和缺乏营养的培养基中无限生长期间以及在受碳源限制的恒化器生长期间，对大肠杆菌对利福平的敏感性进行了测定。在低浊度的分批培养期间，细菌的敏感性随着生长速率的降低而增加，这与在较差培养基中药物渗透可用时间较长一致。在恒化器培养期间，细菌保持高度敏感或产生遗传抗性，这取决于细菌接触抗生素的方式。如果利福平的浓度突然升高，敏感细胞会被遗传抗性细胞取代。然而，如果抗生素浓度缓慢升高，遗传敏感细胞会继续生长。恒化器培养物根据药物给药方式的这种反应差异归因于细菌对药物的诱导解毒作用，因为只有当利福平浓度逐渐增加且维持高细胞群体时，敏感基因型才得以维持。本文提供了从培养上清液的生物测定中获得的利福平失活的直接证据。
