Diversity within Species: Mechanisms, Evolution and Implications in Bacterial Disease

The Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium Escherichia coli are ubiquitous commensal and opportunistic pathogens. In humans, S. aureus is commonly found on the skin and mucus membranes, and is known to cause infections in the skin, bloodstream and brain. E. coli is a normal part of the gut microbiota in humans and can cause intestinal and extraintestinal infections alike. S. aureus and E. coli pose global threats to public health, due to the high morbidity and mortality of invasive strains. The wide range of infections they cause in humans and other animals are exacerbated by the presence of antimicrobial resistance (AMR). Evolutionary processes, like mutation and horizontal gene transfer, are mechanisms through which AMR can arise and spread within a population. These processes, in addition to natural selection and genetic drift, shape the genomic diversity of these pathogens. In this dissertation, I investigate the genetic and evolutionary factors that shape the population of AMR in S. aureus and E. coli. I examine the accessory genomes of publicly available S. aureus genomes to assess gene gain, loss and co-occurrence (Chapter 1), the variation and frequency in genetic recombination of bloodstream E. coli (Chapter 2), and plasmid sharing in human- and animal-associated S. aureus (Chapter 3). The findings of this dissertation provide important insights into the genetic basis for the success of bacterial pathogens, which will inform efforts to treat bacterial diseases and control the spread of AMR.