AbstractDissemination of bacterial clones carrying plasmid-mediated resistance genes is a major factor contributing to the increasing prevalence of antibiotic resistance. Understanding the evolution of successful clones and the association to mobile resistance elements are therefore crucial. In this study, we determined the sequence of a 145 kb IncC multi-drug resistance plasmid (pK71-77-1-NDM), harbouring resistance genes to last-resort antibiotics including carbapenems. We show that the plasmid is able to transfer into a range of genetically diverse clinical Escherichia coli strains and that the fitness cost imposed on the host is often low. Moreover, the plasmid is stably maintained under non-selective conditions across different genetic backgrounds. However, we also observed a lower conjugation frequency and higher fitness cost in the E. coli sequence type (ST) 73 background, which could partially explain why this clone is associated with a lower level of antibiotic resistance than other E. coli clones. This is supported by a bioinformatical analysis showing that the ST73 background harbours plasmids less frequently than the other studied E. coli STs. Studying the evolution of antibiotic resistance in a clinical context and in diverse genetic backgrounds improves our understanding of the variability in plasmid-host associations.