title: Environmental variation alters the fitness effects of rifampicin resistance mutations in Pseudomonas aeruginosa.
abstract: The fitness effects of antibiotic resistance mutations in antibiotic-free conditions play a key role in determining the long-term maintenance of resistance. Although resistance is usually associated with a cost, the impact of environmental variation on the cost of resistance is poorly understood. Here, we test the impact of heterogeneity in temperature and resource availability on the fitness effects of antibiotic resistance using strains of the pathogenic bacterium Pseudomonas aeruginosa carrying clinically important rifampicin resistance mutations. Although the rank order of fitness was generally maintained across environments, fitness effects relative to the wild type differed significantly. Changes in temperature had a profound impact on the fitness effects of resistance, whereas changes in carbon substrate had only a weak impact. This suggests that environmental heterogeneity may influence whether the costs of resistance are likely to be ameliorated by second-site compensatory mutations or by reversion to wild-type rpoB. Our results highlight the need to consider environmental heterogeneity and genotype-by-environment interactions for fitness in models of resistance evolution.
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX13PS, United Kingdom. danna.gifford@zoo.ox.ac.uk.
authors.forename: Danna R
authors.initials: DR
authors.lastname: Gifford
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX13PS, United Kingdom.
authors.forename: Ethan
authors.initials: E
authors.lastname: Moss
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX13PS, United Kingdom.
authors.forename: R Craig
authors.initials: RC
authors.lastname: MacLean
mesh_terms: D005075:Biological Evolution; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D024881:Drug Resistance, Bacterial; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D012293:Rifampin / Q000494:pharmacology*; D013696:Temperature
chemical_list: D012321:DNA-Directed RNA Polymerases; D012293:Rifampin
keywords: Adaptation; antibiotic resistance; bacteria; fitness