Genomic analysis reveals distinct concentration-dependent evolutionary trajectories for antibiotic resistance in Escherichia coli.
Bottom Line: A second class of mutations, recovered only during evolution in higher sublethal concentrations of the antibiotic, deleted the C-terminal end of the ATP synthase shaft.This mutation confers basal-level resistance to kanamycin while showing a strong growth defect in the absence of the antibiotic.In conclusion, the early dynamics of the development of resistance to an aminoglycoside antibiotic is dependent on the levels of stress (concentration) imposed by the antibiotic, with the evolution of less costly variants only a matter of time.
Affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bellary Road, Bangalore, Karnataka 560065, India email@example.com firstname.lastname@example.org.Show MeSH
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Mentions: To characterize the mutational trajectories taken by E. coli towards increased resistance in 4-kan, we performed deep sequencing of the (meta-)genomes of the bacterial populations at various time points during growth in the antibiotic. Two biological replicate cultures were analysed. We performed gDNA sequencing at high temporal resolution for the P0 culture (Fig. 3A). As mentioned earlier, over the course of this culture, the MIC increased ∼2-fold from the basal level. As a control, growth was monitored in an antibiotic-free medium and gDNA sequenced from mid-exponential- and stationary-phase populations. For subsequent dilutions into antibiotic-containing media (P1, P2, etc.), sequencing was performed after entry into stationary phase.Figure 3.
Affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bellary Road, Bangalore, Karnataka 560065, India email@example.com firstname.lastname@example.org.