The molecular epidemiology of bla-CTX-M antibiotic resistance genes in the faecal microbiome of humans acquiring extended-spectrum beta lactamase-producing escherichia coli

Bevan, Edward Robert ORCID: 0000-0002-1272-5506 (2019). The molecular epidemiology of bla-CTX-M antibiotic resistance genes in the faecal microbiome of humans acquiring extended-spectrum beta lactamase-producing escherichia coli. University of Birmingham. Ph.D.

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Abstract

ESBL prevalence is increasing globally and travellers visiting South Asia have high rates of acquisition of CTX-M-producing-E. coli (CTX-M-EC). A prospective observational cohort study of volunteers traveling from the UK to South Asia was undertaken to determine the mechanism of CTX-M-producing E. coli (CTX-M-EC) acquisition. CTX-M-EC was acquired by 16/18 (89%) of volunteers, and polyclonal acquisition of CTX-M-EC was seen in 8/15 volunteers, suggesting multiple acquisition events during travel. CTX-M-EC clones were detectable in faecal samples at six months after travel for 6/6 volunteers. Indistinguishable pre-travel non-CTX-M-EC were found in post-travel faecal samples after CTX-M-EC had been lost in 5/15 cases. Therefore, pre-travel non-CTX-M E. coli remain as a minority population in the gut until the CTX-M-EC are lost. Ten plasmids were sequenced using WGS with short and long reads. Plasmid transfer after filter-mating occurred in CTX-M-EC from 45% of volunteers, suggesting that conjugation also has a role in the human gut. However, in-vivo horizontal transfer of a blaCTX-M plasmid was not detected. Plasmids are closely related to those previously sequenced, isolated from humans, animals and the natural environment. Determining the mechanism of spread of CTX-M-EC will underpin infection prevention and control practices, lay a foundation for future research, and avert excess mortality in the future.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):