Adaptation at different points along antibiotic concentration gradients

From The Royal Society via Jisc Publications RouterHistory: received 2020-12-29, accepted 2021-04-19, collection 2021-05, pub-electronic 2021-05-12Article version: VoRPublication status: PublishedFunder: H2020 European Research Council; Id: http://dx.doi.org/10.13039/100010663; Grant(s): 250152, 268540Funder: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung; Id: http://dx.doi.org/10.13039/501100001711; Grant(s): 155866Funder: Wellcome Trust Royal Society; Grant(s): 216779/Z/19/ZAntibiotic concentrations vary dramatically in the body and the environment. Hence, understanding the dynamics of resistance evolution along antibiotic concentration gradients is critical for predicting and slowing the emergence and spread of resistance. While it has been shown that increasing the concentration of an antibiotic slows resistance evolution, how adaptation to one antibiotic concentration correlates with fitness at other points along the gradient has not received much attention. Here, we selected populations of Escherichia coli at several points along a concentration gradient for three different antibiotics, asking how rapidly resistance evolved and whether populations became specialized to the antibiotic concentration they were selected on. Populations selected at higher concentrations evolved resistance more slowly but exhibited equal or higher fitness across the whole gradient. Populations selected at lower concentrations evolved resistance rapidly, but overall fitness in the presence of antibiotics was lower. However, these populations readily adapted to higher concentrations upon subsequent selection. Our results indicate that resistance management strategies must account not only for the rates of resistance evolution but also for the fitness of evolved strains