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Mol Biol Evol. 2014 Sep;31(9):2387-401. doi: 10.1093/molbev/msu191. Epub 2014 Jun 24.

Strength of selection pressure is an important parameter contributing to the complexity of antibiotic resistance evolution.

Author information

1
Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
2
Department of Ecology and Evolutionary Biology, University of California, Los Angeles.
3
Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey erdaltoprak@sabanciuniv.edu erdaltoprak@gmail.com.

Abstract

Revealing the genetic changes responsible for antibiotic resistance can be critical for developing novel antibiotic therapies. However, systematic studies correlating genotype to phenotype in the context of antibiotic resistance have been missing. In order to fill in this gap, we evolved 88 isogenic Escherichia coli populations against 22 antibiotics for 3 weeks. For every drug, two populations were evolved under strong selection and two populations were evolved under mild selection. By quantifying evolved populations' resistances against all 22 drugs, we constructed two separate cross-resistance networks for strongly and mildly selected populations. Subsequently, we sequenced representative colonies isolated from evolved populations for revealing the genetic basis for novel phenotypes. Bacterial populations that evolved resistance against antibiotics under strong selection acquired high levels of cross-resistance against several antibiotics, whereas other bacterial populations evolved under milder selection acquired relatively weaker cross-resistance. In addition, we found that strongly selected strains against aminoglycosides became more susceptible to five other drug classes compared with their wild-type ancestor as a result of a point mutation on TrkH, an ion transporter protein. Our findings suggest that selection strength is an important parameter contributing to the complexity of antibiotic resistance problem and use of high doses of antibiotics to clear infections has the potential to promote increase of cross-resistance in clinics.

KEYWORDS:

antibiotic resistance; antibiotic susceptibility; cross-resistance; evolution; genotyping; whole-genome sequencing

PMID:
24962091
PMCID:
PMC4137714
DOI:
10.1093/molbev/msu191
[Indexed for MEDLINE]
Free PMC Article

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