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

Qi, Qin and Toll-Riera, Macarena and Heilbron, Karl and Preston, Gail M and MacLean, R Craig (2016) The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa. Proceedings of the Royal Society of London Series B Biological Sciences, 283. Article No. 1822. ISSN 0962-8452

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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 transcriptional regulator gene lasR. Even though the importance of compensatory evolution in maintaining resistance has been widely recognized, our study shows that the roles of general adaptation in maintaining resistance should not be underestimated and highlights the need to understand how selection at other sites in the genome influences the dynamics of resistance alleles in clinical settings.

Item Type: Article
DOI: 10.1098/rspb.2015.2452
Uncontrolled Keywords: Experimental Evolution, whole-genome sequencing, rifampicin resistance, compensatory adaptation, general adaptation
Subjects: 500 Science > 570 Life sciences; biology
Research Group: Bollenbach Group
SWORD Depositor: Sword Import User
Depositing User: Sword Import User
Date Deposited: 11 Feb 2016 16:07
Last Modified: 05 Sep 2017 09:39

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