Investigating enteroaggregative Escherichia coli virulence factors in human intestinal infection

Ellis, Samuel (2018) Investigating enteroaggregative Escherichia coli virulence factors in human intestinal infection. Doctoral thesis, University of East Anglia.

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Abstract

Enteroaggregative Escherichia coli (EAEC) are a major cause of diarrhoeal illness in children, travellers, and the immunocompromised, and associated with foodborne outbreaks worldwide. However, EAEC is a heterogeneous pathotype with frequent asymptomatic carriage and a diversity of virulence factors. Previous studies have been unsuccessful in identifying genetic virulence markers. In this study, two complimentary approaches were applied using intestinal infection models to investigate bacterial factors contributing to EAEC pathogenesis in the human gut.

Firstly, the influence of intestinal environmental signals on the expression of putative EAEC virulence genes was evaluated using a vertical diffusion chamber (VDC). Aerobic oxygen levels increased expression of the adhesins aggregative adherence fimbriae II (AAF/II) and E. coli common pilus, the colonisation factor dispersin, and the global transcriptional activator AggR in prototype strain 042. Furthermore, adherence to polarised T84 intestinal epithelial cells significantly enhanced the expression of adherence factors (AAFs and dispersin), toxins (HlyE, EAST-1, Pet) and the Pic mucinase. This induction required host cell binding and was independent of AggR regulation. Based on these findings, it is proposed that EAEC adherence factors are induced by proximity to the oxygen diffusion gradient across the gut epithelium, while epithelial cell contact activates expression of further virulence factors.

As an alternative approach to identify EAEC pathogenicity markers, virulence-associated phenotypes and genotypic profiles were determined for EAEC sequence types associated with disease (ST40) or carriage (ST31). ST40 isolates exhibited significantly higher biofilm formation and adherence to T84 cells and human colonic biopsies. The genotype comparison identified differences in virulence genes associated with epithelial colonisation and induction of host inflammatory responses between both sequence types.

Overall, this project has revealed that EAEC virulence gene expression is modulated by intestinal environmental signals and identified phenotypic and genotypic traits specific for EAEC sequence types associated with disease or carriage.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Jennifer Whitaker
Date Deposited: 14 Feb 2019 14:06
Last Modified: 14 Feb 2019 14:06
URI: https://ueaeprints.uea.ac.uk/id/eprint/69931
DOI:

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