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

Tugce Oz, Aysegul Guvenek, Sadik Yildiz, Enes Karaboga, Yusuf Talha Tamer, Nirva Mumcuyan, Vedat Burak Ozan, Gizem Hazal Senturk, Murat Cokol, Pamela Yeh, Erdal Toprak

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

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 andmildly 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 becamemore 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.

Original languageEnglish (US)
Pages (from-to)2387-2401
Number of pages15
JournalMolecular biology and evolution
Volume31
Issue number9
DOIs
StatePublished - Sep 2014

Keywords

  • Antibiotic resistance
  • Antibiotic susceptibility
  • Cross-resistance
  • Evolution
  • Genotyping
  • Whole-genome sequencing

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

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