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 language | English |
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Article number | 20160151 |
Number of pages | 8 |
Journal | Proceedings of the Royal Society of London. B, Biological Sciences |
Volume | 283 |
Issue number | 1830 |
DOIs | |
Publication status | Published - 11 May 2016 |
Keywords
- antibiotic resistance
- fitness costs
- genetic background
- Pseudomonas
- RIFAMPICIN-RESISTANCE
- BIOLOGICAL COST
- EVOLUTION
- ENVIRONMENT
- PHYLOGENIES
- LANDSCAPE
- BACTERIA
Profiles
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Thomas Vogwill
- Biological Sciences, Aberdeen Centre For Environmental Sustainability - Research Fellow
- Earth Systems and Environmental Sciences
Person: Academic Related - Research