Antimicrobial resistance and gene regulation in Enteroaggregative Escherichia coli.


   College of Health and Life Sciences

This project is no longer listed on FindAPhD.com and may not be available.

Click here to search FindAPhD.com for PhD studentship opportunities
  Dr Douglas Browning  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Enteroaggregative Escherichia coli (EAEC) is a major cause of diarrhoeal disease in industrialized and non-industrialized countries and has been shown to be the cause of travellers’ diarrhoea and persistent diarrhoea in children and HIV patients. EAEC strains cause disease by binding to the human gastric mucosa and establishing a thick mucoid biofilm, damaging tissue by secreting various toxins [1]. In spite of their widespread occurrence and impact on human health, little is known about how EAEC strains control the expression of genes required to establish infection and cause disease. Furthermore, EAEC strains are increasingly resistant to many clinical antibiotics, decreasing treatment options [1-4]. Thus, there is a need to understand EAEC pathology and devise new methods to combat this important group of bacterial pathogens.

In many EAEC strains, the expression of important virulence determinants (e.g., the attachment adherence fimbriae (AAF) required for colonization, the anti-aggregative protein dispersin (Aap) and its dedicated secretion system) is controlled by the AggR transcription factor, the master regulator of virulence [1-3]. Recently, we have been working with EAEC strains isolated from Egyptian and Brazilian children with diarrhoea [3,4]. In these strains, we have found a new version of AggR that controls gene expression differently. Thus, the main aim of this project will be to determine how this version of AggR controls virulence and determine the genes that it regulates. We have already had the genomes of many of these strains fully sequenced, and so part of this project will be to analyse their genomes to determine each strains characteristics (e.g., antibiotic resistance gene profile, virulence determinants and plasmid replicons etc.). The project will also use synthetic biology to engineer and deliver mutant versions of AggR into EAEC cells, blocking specific promoters and virulence gene expression, as a potential therapeutic approach to combating EAEC infection.

Estimated yearly cost of consumables

£5000

Person Specification

 A Masters degree in a relevant subject with a 60% or higher weighted average, and/or a First or Upper Second Class Honours degree (or an equivalent qualification from an overseas institution)

 Submitting an application

 As part of the application, you will need to supply:

·        A copy of your current CV

·        Copies of your academic qualifications for your Bachelor degree, and Masters degree (if studied); this should include both certificates and transcripts, and must be translated in to English

·        A research proposal statement*

·        Two academic references

·        Proof of your English Language proficiency

 Details of how to submit your application can be found here

 *The application must be accompanied by a “research proposal” statement. An original proposal is not required as the initial scope of the project has been defined, candidates should take this opportunity to detail how their knowledge and experience will benefit the project and should also be accompanied by a brief review of relevant research literature.

 Please include the supervisor’s name and project title in your Personal Statement.

 If you require further information about the application process please contact the Postgraduate Admissions team at [Email Address Removed]


Biological Sciences (4)

Funding Notes

There is no funding for this project.

References

1) Harrington, S.M., Dudley, E.G. and Nataro, J.P. (2006) Pathogenesis of enteroaggregative Escherichia coli infection. FEMS Microbiol Lett. 254(1):12-8. Review.
2*) Yasir, M., Icke, C., Abdelwahab, R., Haycocks, J.R., Godfrey, R.E., Sazinas, P., Pallen, M.J., Henderson, I.R., Busby S.J.W. and Browning, D.F. (2019) Organization and architecture of AggR-dependent promoters from Enteroaggregative Escherichia coli. Molecular Microbiology. 111:534-551.
3*) Abdelwahab, R., Yasir, M., Godfrey, R.E., Christie, G.S., Element, S.J., Saville, F., Hassan, E.A., Ahmed, E.H., Abu-Faddan, N.H., Daef, E.A., Busby, S.J.W. and Browning, D.F. (2021) Antimicrobial resistance and gene regulation in Enteroaggregative Escherichia coli from Egyptian children with diarrhoea: similarities and differences. Virulence 12:57-74
4*) França, F.L.S., Wells, T.J, Browning, D.F., Nogueira, R.T., Sarges, F.S., Pereira, A. C., Cunningham, A.F., Lucheze, K., Rosa, A.C.P., Henderson, I.R. and das Graças de Luna, M. (2013) Genotypic and phenotypic characterisation of enteroaggregative Escherichia coli from children in Rio de Janeiro, Brazil. PLOS ONE 10.1371/journal.pone.0069971.