A study of colonisation of the human gastrointestinal tract by multidrug resistant Escherichia coli

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Snaith, Ann Elisabeth (2023). A study of colonisation of the human gastrointestinal tract by multidrug resistant Escherichia coli. University of Birmingham. Ph.D.

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Abstract

Escherichia coli is a commensal organism recognised as a globally important pathogen as it can cause severe invasive disease, including meningitis and bacteraemia. E. coli is a known carrier of antimicrobial resistance (AMR) and is a major contributor to the global spread of AMR. Mobile genetic elements (MGEs), including plasmids and insertion sequence (IS) elements, are reported to play a crucial role in the spread of AMR and in the creation of multidrug resistant (MDR) organisms. The occurrence of MDR organisms, including MDR E. coli, is a cause of significant concern as it restricts treatment options, and increases patient morbidity and mortality. International travel and hospital admissions often result in increased colonisation with MDR organisms, and both are known to contribute to the global spread of AMR.

Colonisation with drug resistant organisms is a potential route of AMR spread which has not been previously characterised during a traveller stay and there is limited information on colonisation in a hospital inpatient stay. Historical studies of clinical isolates have previously been used to demonstrate the impact of the discovery and increased use of antimicrobials on the rise of AMR, particularly in the last few decades. Previous historical studies have focussed on adult populations which are more likely to have had exposure to a wide range of antimicrobials over longer periods of time. This thesis is a study of E. coli in three different settings. It looks at MDR E. coli colonising healthy travellers to Laos and UK intensive care unit patients, and E. coli causing infection in Dutch neonates. The overall aim of this thesis was to understand the dynamics of colonisation with MDR organisms and the dynamics of MDR infection in the absence of antibiotic selection. Colonisation and infection with MDR E. coli both in the absence of antibiotic selection can improve understanding of AMR in general with no bias to a resistance driven by a specific antibiotic.

Strain level sampling methods in combination with short and long read whole genome sequencing (WGS) were used to explore E. coli from these three different settings. Bioinformatic analysis highlighted key sequence types (STs), AMR gene and plasmid profiles in the three datasets. These techniques and daily sampling helped to characterise the dynamic nature of E. coli colonisation in travellers to Laos, showing the high level of MDR E. coli present and the rapid acquisition and loss of STs during their traveller stay. Detailed characterisation of the plasmids carried by these MDR E. coli highlighted the diversity of plasmids and the diversity of AMR gene settings within these AMR plasmids. Study of E. coli in ICU patients, demonstrated the presence of persistent colonisation during a hospital stay, and the lack of transmission, AMR carriage and ST diversity, widely differing from the Laos traveller dataset. Strain level analysis revealed circulating strains in the traveller population and lack of circulating strains in the ICU population. The clinical infection E. coli isolated from neonates with meningitis or bloodstream infection (BSI), demonstrated that over 47-years resistance carriage remained surprisingly low but there were interesting changes to the composition of the ST population causing invasive disease, including the loss of a predominant ST, ST567, which had not been previously widely reported.

Overall, this study revealed the different dynamics of the three E. coli populations investigated. Strain level sampling in these relevant settings showed the three very different antimicrobial resistance profiles and different ST populations in the absence of any antibiotic selection.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):