Bacterial evolution of antibiotic hypersensitivity

Viktória Lázár, Gajinder Pal Singh, Réka Spohn, István Nagy, Balázs Horváth, Mónika Hrtyan, Róbert Busa-Fekete, Balázs Bogos, Orsolya Méhi, Bálint Csörgo, György Pósfai, Gergely Fekete, Balázs Szappanos, Balázs Kégl, Balázs Papp, Csaba Pál

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147 Citations (Scopus)


The evolution of resistance to a single antibiotic is frequently accompanied by increased resistance to multiple other antimicrobial agents. In sharp contrast, very little is known about the frequency and mechanisms underlying collateral sensitivity. In this case, genetic adaptation under antibiotic stress yields enhanced sensitivity to other antibiotics. Using large-scale laboratory evolutionary experiments with Escherichia coli, we demonstrate that collateral sensitivity occurs frequently during the evolution of antibiotic resistance. Specifically, populations adapted to aminoglycosides have an especially low fitness in the presence of several other antibiotics. Whole-genome sequencing of laboratory-evolved strains revealed multiple mechanisms underlying aminoglycoside resistance, including a reduction in the proton-motive force (PMF) across the inner membrane. We propose that as a side effect, these mutations diminish the activity of PMF-dependent major efflux pumps (including the AcrAB transporter), leading to hypersensitivity to several other antibiotics. More generally, our work offers an insight into the mechanisms that drive the evolution of negative trade-offs under antibiotic selection.

Original languageEnglish
Article number700
JournalMolecular systems biology
Publication statusPublished - Oct 29 2013


  • Antibiotic resistance
  • collateral sensitivity network
  • evolutionary experiment
  • trade off

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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  • Cite this

    Lázár, V., Pal Singh, G., Spohn, R., Nagy, I., Horváth, B., Hrtyan, M., Busa-Fekete, R., Bogos, B., Méhi, O., Csörgo, B., Pósfai, G., Fekete, G., Szappanos, B., Kégl, B., Papp, B., & Pál, C. (2013). Bacterial evolution of antibiotic hypersensitivity. Molecular systems biology, 9, [700].