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Understanding the virulence and resistance of Escherichia coli in different countries

Almusallam, Abdulrahman 2023. Understanding the virulence and resistance of Escherichia coli in different countries. PhD Thesis, Cardiff University.
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Escherichia coli is the most prototypical bacteria known by laymen, while also being the most extensively studied of the prokaryotes (due in part to its being the genetic workhorse of molecular biology). Yet, it is quite remarkable how there is still so much to learn about this organism. Throughout this report, I hope to demonstrate that there are still merits to be found in macro and micro observations of E. coli’s genetics, distribution, and behaviour. Although each chapter within this report exists as an independent entity, the unifying theme is that of extended-spectrum β-lactamase (ESBL) resistance within E. coli and its common occurrence with pathogenic strains. The choice of this theme is simple: ESBLs are the most successful and important resistance mechanisms in E. coli. The importance of ESBLs in E. coli cannot be understated. E. coli is a common bacterial agent of infection, and upon acquisition of an ESBL, infection can become very difficult to treat. This is firstly because the ESBL provides protection against penicillins and most cephalosporins, which are typically the gold standard for a broad-spectrum treatment against infection and secondly that ESBLs are often accompanied by other resistance mechanisms in dominant individual strains of E. coli, such as ST131. E. coli is such a ubiquitous organism and so historic in its study that many papers have been published using various cohorts of isolates. Within this report exists a comprehensive analysis of past E. coli literature, and through this scrutiny, I chose contemporary strains of E. coli that are routinely carried in the human gut in several different nations. I specifically utilised a previously archived library of E. coli captured across the UK in 2014 as a part of a wider Public Health England study (n= 300) and sampled from five different geographic regions across the UK, including both human carriage isolates as well as those causing serious disease. It was these isolates that made up the body of work presented in Chapter 3. The 2014 study sought to understand the epidemiology of resistant E. coli across the UK and genotypically compare isolates found in bacteraemia, faeces, sewage, and meat. Interestingly, the study found that resistant E. coli associated with meat was unique and separate from those found in bacteraemia and human carriage. All the isolates captured as a part of this 2014 study were grown on antibiotic-selective media, thereby creating a bias in selection. Additionally, one of the key observations of this study was that the proportions of E. coli sequence types between blood isolates, faecal isolates, and sewage isolates were very similar. This led to the natural question of what types of E. coli are associated with human carriage when antibiotic selection is removed? And since this 2014 study had also shown the strength of sewage as a measure of both faecal carriage and subsequent disease: we utilised sewage across the UK to address these questions. Sampling two sites in South Wales, one in Bristol, and three near London, a library of some 600 E. coli isolates was generated (approximately 100 isolates per site) without antibiotic bias and representing common E. coli types that are carried by the human population at these different locations. This collection serves as a unique snapshot of E. coli’s pathogenicity, resistance, and prevalence in the UK. This body of work demonstrates how variable levels of E. coli bacteraemia rates across the UK are directly related to higher or lower carriage of pathogenic E. coli types by local populations and E. coli sepsis rates will likely be ineffective until this is acknowledged. Simultaneous to the UK sewage work, through my own initiative and our international collaborations, we collected sewage from Kazakhstan, Saudi Arabia, and Bangladesh. The E. coli libraries created from these samples were again simple in their design. For each site, sewage samples were grown on selective and nonselective media to get an accurate representation of the E. coli associated with human carriage in 2019 from various parts of the world. Where possible, whole genome sequencing was utilised to definitively interrogate these organisms and shed light upon E. coli’s true hylogenetic composition in the different national locations. Within this body of work, I believe I have provided the most comprehensive analysis of chromosomal and plasmid insertions of blaCTX-M-15 to date for E. coli. This has demonstrated the huge importance of the chromosomal carriage of this particular resistance mechanism and has also highlighted the chromosomal carriage of other important resistance mechanisms. Equally, I believe my 2019 cohort of some 600 isolates captured across the UK without selection stands as one of the most complete archives of human E. coli carriage to date and has shed an important light on the enigma of the rising E. coli sepsis rates in the UK. Finally, the collections of strains from different nations have demonstrated that the E. coli types circulating in the different nations can be manipulated using antibiotics to select more pathogenic phylotypes. Thus, the use of antibiotics can not only increase antibiotic resistance rates but also increase pathogenic types leading to increased sepsis rates.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 14 March 2024
Last Modified: 14 Mar 2024 14:22

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