Evolution of Resistance to Continuously Increasing Streptomycin Concentrations in Populations of Escherichia coli

ABSTRACT The evolution of antibiotic resistance in bacteria has become one of the defining problems in modern biology. Bacterial resistance to antimicrobial therapy threatens to eliminate one of the pillars of the practice of modern medicine. Yet, in spite of the importance of this problem, only recently have the dynamics of the shift from antibiotic sensitivity to resistance in a bacterial population been studied. In this study, a novel chemostat method was used to observe the evolution of resistance to streptomycin in a sensitive population of Escherichia coli, which grew while the concentration of antibiotic was constantly increasing. The results indicate that resistant mutants remain at a low frequency for longer than expected and do not begin to rise to a high frequency until the antibiotic concentrations are above the measured MIC, creating a “lull period” in which there were few bacterial cells growing in the chemostats. Overall, mutants resistant to streptomycin were found in >60% of the experimental trial replicates. All of the mutants detected were found to have MICs far above the maximum levels of streptomycin to which they were exposed and reached a high frequency within 96 h.