Strong Environment-Genotype Interactions Determine the Fitness Costs of Antibiotic Resistance In Vitro and in an Insect Model of Infection

The acquisition of antibiotic resistance commonly imposes fitness costs, a reduction in the fitness of bacteria in the absence of drugs. These costs have been quantified primarily using experiments and a small number of studies in mice, and it is commonly assumed that these diverse methods are consistent. Here, we used an insect model of infection to compare the fitness costs of antibiotic resistance to those Experiments explored diverse mechanisms of resistance in a Gram-positive pathogen, , and a Gram-negative intestinal symbiont, Rifampin resistance in showed fitness costs that were typically elevated although these were modulated by genotype-environment interactions. In contrast, resistance to cefotaxime via derepression of AmpC β-lactamase in resulted in no detectable costs or , while spontaneous resistance to nalidixic acid, and carriage of the IncP plasmid RP4, imposed costs that increased Overall, fitness costs were a poor predictor of fitness costs because of strong genotype-environment interactions throughout this study. Insect infections provide a cheap and accessible means of assessing the fitness consequences of resistance mutations, data that are important for understanding the evolution and spread of resistance. This study emphasizes that the fitness costs imposed by particular mutations or different modes of resistance are extremely variable and that only a subset of these mutations is likely to be prevalent outside the laboratory.