Limited Evolutionary Conservation of the Phenotypic Effects of Antibiotic Resistance Mutations

Gábor Apjok, Gábor Boross, Ákos Nyerges, Gergely Fekete, Viktória Lázár, Balázs Papp, Csaba Pál, Bálint Csörgo, Miriam Barlow

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Multidrug-resistant clinical isolates are common in certain pathogens, but rare in others. This pattern may be due to the fact that mutations shaping resistance have species-specific effects. To investigate this issue, we transferred a range of resistance-conferring mutations and a full resistance gene into Escherichia coli and closely related bacteria. We found that resistance mutations in one bacterial species frequently provide no resistance, in fact even yielding drug hypersensitivity in close relatives. In depth analysis of a key gene involved in aminoglycoside resistance (trkH) indicated that preexisting mutations in other genes - intergenic epistasis - underlie such extreme differences in mutational effects between species. Finally, reconstruction of adaptive landscapes under multiple antibiotic stresses revealed that mutations frequently provide multidrug resistance or elevated drug susceptibility (i.e., collateral sensitivity) only with certain combinations of other resistance mutations. We conclude that resistance and collateral sensitivity are contingent upon the genetic makeup of the bacterial population, and such contingency could shape the long-term fate of resistant bacteria. These results underlie the importance of species-specific treatment strategies.

Original languageEnglish
Pages (from-to)1601-1611
Number of pages11
JournalMolecular biology and evolution
Volume36
Issue number8
DOIs
Publication statusPublished - Aug 1 2019

Keywords

  • Antibiotic resistance
  • Collateral sensitivity
  • Evolution of mutational effects
  • Multidrug resistance

ASJC Scopus subject areas

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

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