Chairs: Rowan Casey and David Mark

The emergence and spread of antimicrobial resistance poses a considerable risk to human health and the ability to successfully treat bacterial infections. Classical adaptative evolution experiments in which single-species cultures of bacterial pathogens are exposed to antibiotics in rich laboratory media have allowed us to establish a fundamental knowledge of antibiotic resistance mechanisms. But it is clear these laboratory cultures fall short of representing the complexity of the biological environments where infections occur. The use of infection-niche mimicking media provides a simple solution to bridge this gap and more accurately represent the nutrient environment of the infection niche, without the use of animal models. Here we tested the impact of infection-niche mimicking media, modelled on the environment of acute respiratory infection, on the evolution of meropenem resistance in Pseudomonas aeruginosa. P. aeruginosa is an opportunistic bacterial pathogen that can cause severe lung infections in immunocompromised patients. An adaptive laboratory evolution experiment was carried out to investigate the evolution of meropenem resistance in Pseudomonas aeruginosa in this respiratory-mimicking media compared to rich laboratory tryptic soy broth. Differences in the evolvability of meropenem resistance, as well as in the meropenem concentrations tolerated by endpoint isolates, were observed between respiratory-mimicking media and tryptic soy broth. Genome sequencing, minimum inhibitory concentration assays and fitness assays of the evolved endpoint isolates have allowed us to build a picture of differences in meropenem evolvability and evolutionary trajectories by which resistance is achieved when using respiratory-mimicking media compared to rich laboratory media.