{"issue":"1822","date_published":"2016-01-13T00:00:00Z","publication_status":"published","abstract":[{"lang":"eng","text":"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."}],"department":[{"_id":"ToBo"}],"day":"13","file":[{"content_type":"application/pdf","file_name":"IST-2016-488-v1+1_20152452.full.pdf","creator":"system","access_level":"open_access","relation":"main_file","checksum":"78ffe70c1c88af3856d31ca6b7195a27","file_id":"4899","date_created":"2018-12-12T10:11:43Z","file_size":626804,"date_updated":"2020-07-14T12:45:02Z"}],"type":"journal_article","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"date_updated":"2021-01-12T06:51:33Z","month":"01","status":"public","title":"The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa","quality_controlled":"1","date_created":"2018-12-11T11:52:40Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa":1,"oa_version":"Published Version","scopus_import":1,"publisher":"Royal Society, The","citation":{"ieee":"Q. Qi, M. Toll Riera, K. Heilbron, G. Preston, and R. C. Maclean, “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, vol. 283, no. 1822. Royal Society, The, 2016.","mla":"Qi, Qin, et al. “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, vol. 283, no. 1822, 20152452, Royal Society, The, 2016, doi:10.1098/rspb.2015.2452.","short":"Q. Qi, M. Toll Riera, K. Heilbron, G. Preston, R.C. Maclean, Proceedings of the Royal Society of London Series B Biological Sciences 283 (2016).","ama":"Qi Q, Toll Riera M, Heilbron K, Preston G, Maclean RC. 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. 2016;283(1822). doi:10.1098/rspb.2015.2452","ista":"Qi Q, Toll Riera M, Heilbron K, Preston G, Maclean RC. 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(1822), 20152452.","chicago":"Qi, Qin, Macarena Toll Riera, Karl Heilbron, Gail Preston, and R Craig Maclean. “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. Royal Society, The, 2016. https://doi.org/10.1098/rspb.2015.2452.","apa":"Qi, Q., Toll Riera, M., Heilbron, K., Preston, G., & Maclean, R. C. (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. Royal Society, The. https://doi.org/10.1098/rspb.2015.2452"},"pubrep_id":"488","language":[{"iso":"eng"}],"article_number":"20152452","_id":"1552","doi":"10.1098/rspb.2015.2452","has_accepted_license":"1","publication":"Proceedings of the Royal Society of London Series B Biological Sciences","author":[{"id":"3B22D412-F248-11E8-B48F-1D18A9856A87","full_name":"Qi, Qin","last_name":"Qi","first_name":"Qin","orcid":"0000-0002-6148-2416"},{"first_name":"Macarena","last_name":"Toll Riera","full_name":"Toll Riera, Macarena"},{"last_name":"Heilbron","first_name":"Karl","full_name":"Heilbron, Karl"},{"first_name":"Gail","last_name":"Preston","full_name":"Preston, Gail"},{"last_name":"Maclean","first_name":"R Craig","full_name":"Maclean, R Craig"}],"file_date_updated":"2020-07-14T12:45:02Z","acknowledgement":"We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics funded by Wellcome\r\nTrust grant reference 090532/Z/09/Z and Medical Research Council Hub grant no. G0900747 91070 for generation of the high-throughput sequencing data. We thank Wook Kim and two anonymous reviewers for their constructive feedback on previous versions of our manuscript.","ddc":["570"],"publist_id":"5619","volume":283,"intvolume":" 283","year":"2016"}