Plasmid mediated resistance to β-lactam antibiotics in Enterobacteriaceae: mechanisms and detection of plasmid transmission

Abstract

This thesis describes various studies investigating the relationship between plasmids and β-lactam resistance development, the detection of β-lactam resistance in short-read sequence data and the genetic diversity of β-lactam resistance plasmids. Chapter 2 describes 2 studies relating exposure to external DNA to the development of β-lactam resistance through chromosomal mutations in E. coli. Chapter 3 describes a study evaluating the performance of PlasmidSPAdes plasmid assembly of ESBL-producing Enterobacteriaceae in terms of detection of ESBL-encoding genes, plasmid replicons, chromosomal wgMLST genes, and to assess the effect of the k-mer size. Furthermore, chapter 4 presents 3 studies investigating the within patient β-lactam resistance plasmid dynamics during a hospital outbreak and the genetic diversity between epidemiologically unrelated and related resistance plasmids.