Chattaway, MA; (2015) A Novel Approach to Pathogen Recognition for Diarrhoeagenic Enteroaggregative Escherichia coli. Doctoral thesis , UCL (University College London).

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Text Chattaway_Marie Anne Chattaway_PhD Corrected Thesis Final 19.06.2015.pdf. redacted.pdf Download (19MB) | Preview

Abstract

Enteroaggregative E. coli is known to cause diarrhoeal disease in developing and developed countries, but is also found in asymptomatic carriage and so the causal link between EAEC and disease is unknown. This study assessed bacterial load, the presence of co-infections and demographic data to assess if EAEC was independently associated with intestinal infectious disease in the United Kingdom. This study concluded that EAEC was independently capable of causing disease and accounts for ~1% of intestinal disease and therefore an important burden. A case control approach of analysis by multi locus sequence typing of 564 EAEC isolates from cases and controls in Bangladesh, Nigeria and the UK spanning the past 29 years, revealed multiple successful lineages of EAEC. The population structure of EAEC indicates some clusters are statistically associated with disease or carriage, further highlighting the heterogeneous nature of this group of organisms. Different clusters have evolved independently as a result of both mutational and recombination events; the EAEC phenotype is distributed throughout the population of E. coli. In vivo models looking at EAEC infection and virulence gene content of EAEC show that different complexes varied in their ability to cause disease further concluding that these complexes may have come from different ecological niches but that the EAEC phenotype enhanced survival and so these defined EAEC complexes have converged to stably retain the plasmid and phenotype. This study has identified several successful EAEC complexes associated with sporadic disease (ST 10, 38, 40, 295, 278, 394, 678 and 746 Cplx) with subset of complexes showing evidence of patho-adaptation to cause extra-intestinal infections (ST38 Cplx) and outbreaks (ST40, 278 and 678 Cplx) or form hybrid strains with Shiga toxin producing E. coli causing severe disease (ST40 and 678 Cplx).

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