"Antimicrobial resistance is a global public health problem. Bacteria can quickly develop resistance against many of the existing antimicrobials, and consequently prolonged treatment periods lead to human suffering, loss of productivity, and high health care costs. In order to tackle the antibiotic resistance problem, either new antibiotics or methods for using the current collection of antibiotics more efficiently is necessary. Here, I propose an experimental study to uncover the evolution of bacterial drug resistance which I believe will be very valuable for slowing down the spread of resistance by using the currently available antibiotics. The specific aims of this proposal are: (1) Measuring the rates of evolution under single drug and drug combination treatments; (2) Examining pleiotropic effects of (non-drug) stressful conditions on evolution of drug resistance; (3) Measuring the epistatic interactions between mutations that confer antibiotic resistance. We will perform these studies by using high-throughput measurements and a custom made fully automated fluidics system, “the morbidostat”, which can unequivocally follow bacterial evolution in antibiotic environments. Being able to understand the evolution of antibiotic resistance both at the population and enzymatic level, and identifying the pleitropic effects that cause antibiotic resistance will be very helpful for planning interventions to combat antibiotic resistance."