The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa

Proceedings. Biological Sciences
Qin QiR C Maclean

Abstract

Antibiotic resistance carries a fitness cost that must be overcome in order for resistance to persist over the long term. Compensatory mutations that recover the functional defects associated with resistance mutations have been argued to play a key role in overcoming the cost of resistance, but compensatory mutations are expected to be rare relative to generally beneficial mutations that increase fitness, irrespective of antibiotic resistance. Given this asymmetry, population genetics theory predicts that populations should adapt by compensatory mutations when the cost of resistance is large, whereas generally beneficial mutations should drive adaptation when the cost of resistance is small. We tested this prediction by determining the genomic mechanisms underpinning adaptation to antibiotic-free conditions in populations of the pathogenic bacterium Pseudomonas aeruginosa that carry costly antibiotic resistance mutations. Whole-genome sequencing revealed that populations founded by high-cost rifampicin-resistant mutants adapted via compensatory mutations in three genes of the RNA polymerase core enzyme, whereas populations founded by low-cost mutants adapted by generally beneficial mutations, predominantly in the quorum-sensing...Continue Reading

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Citations

Aug 10, 2016·Molecular Biology and Evolution·Andreas PorseMorten O A Sommer
Nov 2, 2016·Journal of Evolutionary Biology·A MacPherson, S L Nuismer
Apr 19, 2017·PLoS Biology·Jorge Moura de SousaIsabel Gordo
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Mar 7, 2017·Frontiers in Microbiology·Alex Wong

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