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Long-term molecular epidemiology of extended-spectrum

β-lactamase-producing Escherichia coli in a low-endemic

setting

av

Anna Fagerström

Akademisk avhandling

Avhandling för medicine doktorsexamen i Medicinsk vetenskap med inriktning Biomedicin,

som kommer att försvaras offentligt fredagen den 20 mars 2020 kl. 09.00, Hörsal C1 Campus USÖ, Örebro universitet

Opponent: Docent Linus Sandegren Uppsala universitet

Örebro universitet

Institutionen för medicinska vetenskaper 701 82 ÖREBRO

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Abstract

Anna Fagerström (2020): Long-term molecular epidemiology of extended-spectrum β-lactamase-producing Escherichia coli in a low-endemic setting. Örebro Studies in Medicine 207.

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 urosep-sis 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 conjuga-tive 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 of-ten 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 envi-ronment 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 line-ages 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 ge-netically similar to those causing infections in humans were present in envi-ronmental waters indicating that transmission of ESBL-producing E. coli from humans to the aquatic environment likely has occurred.

Keywords: Escherichia coli, extended-spectrum β-lactamase, whole genome sequencing, plasmids, hybrid assembly, environment, IncI1, ST131

Anna Fagerström, School of Medical Sciences, Örebro University, SE-70182 Örebro, Sweden, anna.fagerstrom@regionorebrolan.se

References

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