Long-term molecular epidemiology of extended-spectrum β-lactamase producing Escherichia coli in a low-endemic setting

Abstract: Escherichia coli is a commensal inhabitant in the gastro-intestinal tract of humans and animals but it is also the most common bacterial species causing urinary tract infection, which ranges in severity from distal cystitis to urosepsis and septic shock. During the past decades, the prevalence of antibiotic resistant E. coli has increased worldwide. Extended-spectrum β-lactamases (ESBL) causes resistance to β-lactam antibiotics, the most widely used class of antibiotics. The genes encoding ESBL, bla, are usually carried on conjugative plasmids, which can be transferred between different bacterial lineages and different species. These plasmids frequently also carry resistance genes to additional antibiotic classes, and ESBL-producing E. coli are therefore often multidrug-resistant. The aim of this thesis was to describe the long-term molecular epidemiology of ESBL-producing E. coli in Örebro County during the time when they first started to emerge. In addition, potential transmission to the environment was investigated by performing a comparative analysis on ESBL-producing E. coli isolated from patients and from the aquatic environment in Örebro city. In general, the E. coli population was genetically diverse, but the pandemic lineage ST131, first identified in 2004, appears to have been responsible for the dramatic increase of CTX-M-15-producing E.coli observed during the late 2000s. CTX-M-15 was the most prevalent ESBL-type followed by CTX-M-14 and these genes were mainly found on plasmids belonging to the IncF or IncI1 families. Continuous horizontal transmission of IncI1 ST31 and ST37 plasmids between diverse E. coli lineages have also contributed to the dissemination of blaCTX-M-15 in Örebro County. Extended spectrum β-lactamase-producing E. coli were found to be common in the aquatic environment in Örebro city and E. coli lineages genetically similar to those causing infections in humans were present in environmental waters indicating that transmission of ESBL-producing E. colifrom humans to the aquatic environment likely has occurred.