The evolution of plasmid gene content in Enterobacteriaceae

Plasmids are extra-chromosomal genetic elements that play a crucial role in the genome evolution of prokaryotes. Plasmid-encoded genes may be beneficial for their host, e.g., genes encoding antibiotic resistance. In this thesis, I investigated the gene content evolution in plasmid genomes, with a focus on essential and beneficial genes. In chapter one, I asked if plasmid-encoded genes may be essential for the host. For that, I surveyed the presence of essential genes on plasmids in Escherichia coli and found that these are rarely found on plasmids. Through phylogenetic analyses and evolution experiments, we provided a mechanistic explanation of why essential genes are rarely found on plasmids. Our results highlight a barrier to lateral transfer of essential genes from a chromosome to plasmids. In chapter two, I compared the distribution of different antibiotic resistance genes (ARG) between plasmids and chromosomes in Escherichia, Salmonella, and Klebsiella. My results reveal that the function of the encoded resistance mechanisms is an important determinant of gene mobility. In chapter three, I quantified the cumulative impact of transposable elements on the evolution of ARG content in different types of plasmids. My results revealed the trends and barriers to plasmid-mediated ARG transfer and emphasized the important role of transposable elements in generating antibiotic resistance islands in plasmid genomes. Overall, the studies in this thesis unveil several constraints on the evolution of plasmid gene content, and contributions of transposable elements to plasmid genome evolution.