Colonisation of the gut microbiome by Escherichia coli during international travel

Davies, Matthew ORCID: 0000-0002-9752-6273 (2024). Colonisation of the gut microbiome by Escherichia coli during international travel. University of Birmingham. Ph.D.

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Abstract

There is a high risk of acquiring extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E), predominantly Escherichia coli, among international travellers visiting antimicrobial resistance hotspots. Although factors that drastically perturb the gut microbiome — e.g. antibiotic use and travellers’ diarrhoea — have been shown to influence the risk of ESBL-E acquisition, it remains largely unknown whether successful colonisation of ESBL-E during travel is associated with the composition, functional capacity and resilience of the traveller’s microbiome. Strains of E. coli often vary by geography and pathogenicity and it is unknown how their inter- and intra-species interactions associate with the acquisition of ESBL-E. The research in this thesis aims to address these problems by determining how involved the entire gut microbiome is in resisting colonisation from invading ESBL-E, or if species interactions are more important. Faecal samples from before travel and immediately upon return from Africa or Asia of 179 Dutch travellers had previously been collected and whole metagenome shotgun sequenced. Here, the gut microbiome was profiled with a metagenomics species concept approach and the microbial composition, population diversity and functional capacity were determined and how these associate with the acquisition of ESBL-E during travel was calculated. None of the measurements in pre-travel samples were predictive of risk of acquiring ESBL-E. When compared to post-travel measurements, there were also no longitudinal changes specific to acquiring ESBL-E, instead only significantly associating with the onset of travellers’ diarrhoea. How individual taxa are associated was then determined, where it was discovered that the prevalence and abundance of Citrobacter freundii and two members of the genus Bacteroides increased in those remaining uncolonised by ESBL-E, suggesting that these taxa may have some capability of outcompeting ESBL-E. This was tested by growing both commensal and ESBL-producing E. coli in nutrient broth in the presence of travel-acquired Citrobacter, but Citrobacter could not outcompete E. coli in a direct manner in nutrient rich media.
As the longitudinal change to E. coli was not significantly associated with the acquisition of ESBL-producing E. coli, it was hypothesised that strain replacement was occurring. Individual strains were assembled into metagenome assembled genomes (MAGs) and compared to reference genomes that represent the total E. coli strain diversity. The population of E. coli strains was drastically altered during travel, but this was independent from the factors driving the acquisition of ESBL-E (and perturbing the gut microbiome). The results from this thesis highlight the potential of individual species to interact with invading ESBL-E, but most importantly focusses future research towards avenues of altering a person’s colonisation resistance as an intervention strategy to minimise the spread of multidrug resistant bacteria.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):