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: The P0 growth curve of E. coli grown in 4 µg/ml kanamycin (4-kan) is characterized by a long lag phase (6–7 h) followed by an exponential phase defined by low growth rate (Fig. 1A and Supplementary Fig. S3 for statistics). The lag phase period increased considerably to at least 11 h in 8 µg/ml kanamycin (8-kan) (Fig. 1C and Supplementary Fig. S3); the cultures typically reached a final OD after 24 h that was less than what was observed for the 4-kan cultures (compare Fig. 1A and C, and Supplementary Fig. S3B).Figure 1.
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.