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Whole-population genomic sequencing reveals the mutational profiles of the antibiotic-treated Escherichia coli populations

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Abstract

Antibiotic resistance is a major problem for public health worldwide. Since bacteria may rapidly respond to antibiotics and acquire resistance, it is important to understand how the bacterial genome changes under antibiotic treatments. With the advent of high-throughput approaches, experimental limitations in characterizing the roles of new mutations and the selection related to the evolution of antibiotic resistance have been eliminated. Here, to explore the mutation profiles of E. coli populations exposed to sub-inhibitory and then increasing concentrations of the antibiotics norfloxacin and colistin, an evolution experiment was combined with whole-population genomic sequencing. The results showed that, while the occurrence of genome-wide mutations is dramatically higher in the populations that were only treated with norfloxacin, there is a remarkable decrease in the colistin-treated populations compared to norfloxacin. It suggests that antibiotics not only elevate the genome-wide mutation rate but also magnify the rate of occurrence of advantageous mutations that increase the rate of adaptation. This work provides further evidence to support the idea that antibiotics can act indirectly as bacterial mutagens, and also that sequential antibiotic treatments may contribute to acquiring antibiotic resistance by improving the adaptation rate in bacteria in a relatively short time.

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Data availability

Raw sequence data reported in this study has been deposited in NCBI SRA (Bioproject No.: PRJNA727091).

Abbreviations

DNM:

de novo mutation

MDR:

Multi-drug resistant

EE:

Experimental evolution

MIC:

Minimum inhibitory concentration

QRDR:

Quinolone resistance determining region

MW U test:

Mann-Whitney U test

LPS:

Lipopolysaccharides

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Acknowledgments

We thank Ozgur Ozdemirel for technical help. This work is supported by the grant from Hacettepe University Research Fund (FHD-2017-13143).

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Funding

This work is supported by the grant from Hacettepe University Research Fund (FHD-2017-13143).

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Correspondence to Sibel Kucukyildirim.

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Kucukyildirim, S. Whole-population genomic sequencing reveals the mutational profiles of the antibiotic-treated Escherichia coli populations. Biologia 77, 525–531 (2022). https://doi.org/10.1007/s11756-021-00959-8

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  • DOI: https://doi.org/10.1007/s11756-021-00959-8

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