Composition, evolution and transfer of resistance plasmids in Escherichia coli

Resistance plasmids and mobile genetic elements (MGEs) play a crucial role in the transfer of antimicrobial resistance from the veterinary sector to human healthcare. In this thesis, plasmids from foodborne Escherichia coli isolates with a known (ES)BL or tetracycline resistance were sequenced with short- and long-read technologies to obtain insight into their composition. The isolates often contained several plasmids coding for resistance to various antimicrobials. Most plasmids belonged to IncI, IncF and IncX incompatibility groups and contained a conserved and variable region. Clusters containing resistance genes were identified and found in the variable regions as well as the presence of an addiction system. Conjugation experiments were performed with the foodborne E. coli isolates and a common recipient E. coli strain. The physiological and genetic aspects of conjugation were analysed. Conjugation happens in low rates, but transconjugant cells can grow as well as the recipient strain. Longer co-incubation can lead to the spread of more plasmids or resistance genes. The transferred plasmids are explained through selective pressure as only plasmids harbouring an (ES)BL gene transferred successfully. These plasmids show little to no changes when compared to the plasmid in the donor strain. However, in rare cases a plasmid can obtain an extra resistance gene cluster during transfer. Lastly, a multiplicated mobile genetic element containing ampC was discovered upon exposure to amoxicillin that can sometimes transfer to other cells. These outcomes show how dynamic naturally occurring MGEs can transfer antimicrobial resistance and this poses a continuing threat for veterinary and human healthcare.