Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas

T. Vogwill*, M. Kojadinovic, R. C. Maclean

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Citations (Scopus)
1 Downloads (Pure)

Abstract

Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the beta subunit of RNA polymerase (rpoB) across eight strains that span the diversity of the genus Pseudomonas. We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across three strains of Pseudomonas. Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds.

Original languageEnglish
Article number20160151
Number of pages8
JournalProceedings of the Royal Society of London. B, Biological Sciences
Volume283
Issue number1830
DOIs
Publication statusPublished - 11 May 2016

Keywords

  • antibiotic resistance
  • fitness costs
  • genetic background
  • Pseudomonas
  • RIFAMPICIN-RESISTANCE
  • BIOLOGICAL COST
  • EVOLUTION
  • ENVIRONMENT
  • PHYLOGENIES
  • LANDSCAPE
  • BACTERIA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)

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