I have investigated how bacterial viruses (phages) transfer bacterial DNA between cells by a process termed transduction and how this affects the ability of bacteria and phages to survive adverse conditions. In the human pathogen, Staphylococcus aureus I followed transfer of antibiotic resistance genes between cells and found that for phages, that as part of their lifestyle is integrated in the bacterial genome, benefit from transduction of antibiotic resistance genes when the bacteria are exposed to antibiotics. The phages residing in bacterial genomes are termed pro-phages and my work furthermore revealed that bacterial genes affect the stability of prophages. Thus, this suggests that there is close collaboration between phage and bacterium and that these interactions can lead to dissemination of antibiotic resistance genes between bacteria. Overall, the research conducted for this thesis expands the current knowledge on transduction and related processes in S. aureus and it points to a symbiotic relationship between phages and bacteria.

Antibiotic resistance is a major threat to public health, undermining our ability to treat infectious disease. Often, isolates bearing resistance mutations suffer a cost of resistance, that is, lower fitness than their susceptible counterparts. Nonetheless, fitness can be ameliorated by secondary site mutations, known as compensatory mutations. These mutations restore fitness to the normal level without eliminating resistance. Despite the potential importance of compensation for public health strategies to combat antibiotic resistance, relatively little is known about the molecular mechanisms of compensation. Here, we investigate mechanisms of compensation for quinolone resistance mutations in Escherichia coli. We found substantial costs of resistance for two genotypes, derived from MG1655 (K-12): a gyrA D87G mutant, and a marR R94C mutant. Subsequent selection in the absence of antibiotics led to an improvement in fitness, with at least partial retention of quinolone resistance. Whole-genome sequencing was used to identify potential compensatory mutations. Potential compensatory mutations found within essential genes that encode transport systems and transcriptional factors. This work will provide insight into the mechanisms of compensation of the costs of quinolone resistance in Escherichia coli.