Antibiotic resistance is a growing public-health concern. Efforts to control the emergence and spread of resistance would benefit from an improved ability to forecast when and how it will evolve. To predict the evolution of resistance with accuracy, we must understand and integrate information about many factors, including a bacterium’s evolutionary history. In this presentation, I discuss the effects of genetic background on the evolution of phenotypic resistance, its genetic basis, and its fitness costs.

First, I ask how readily bacteria can overcome prior losses of intrinsic resistance through subsequent evolution when challenged with antibiotics. Second, I consider whether lineages founded from different genotypes take parallel or divergent mutational paths to achieve increased resistance. Third, I inquire whether fitness costs of resistance mutations are constant across different genetic backgrounds. In general, I focus attention on the interplay between repeatability and contingency in the evolutionary process. I demonstrate that genetic background can influence both the phenotypic and genotypic evolution of resistance and its associated fitness costs. I conclude this presentation by highlighting clinical and public-health implications of this work.