PhD Study : Boosting antibiotics to fight resistance: Investigating the effects of combining biosurfactants with antibiotics to treat antibiotic resistant pathogens causing Healthcare Associated Infections

Summary

The emergence of ‘superbugs’, bacteria with resistance against many different antibiotics is recognised by the World Health Organisation (WHO) as a global crisis. They are now a frequent complication in healthcare, often endangering successful outcomes of routine medical interventions. Enterococci were considered harmless bacterial members of the gastrointestinal microbiome. However, multi-drug resistant enterococcal infections are now a leading cause of Healthcare Associated Infection (HAI).

A significant concern is the spread of resistance to the antibiotic vancomycin which is a major driver in the generation of multiresistant strains. Enterococcal biofilms pose a significant threat to patient wellbeing because of high levels of antibiotic resistance. New antibiotics have been difficult to find so we need to improve the activity of our current antibiotics. Combining antibiotics with biosurfactants offers the possibility to increase their efficacy and extend their life against resistant bacteria. This is the focus of this project.

Biological assay techniques used in the laboratory can measure bacteria cell death, biofilm disruption and can quantify the efficacy of antimicrobial treatments and the synergy between antimicrobials. However, this does not tell us how the biosurfactants actually work and it is likely that their mode of action may involve modifications of the bacterial surface. Therefore, the combined effect of antibiotics and biosurfactants are best studied using high resolution microscopic techniques such as Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM) which can help visualise the morphological changes in the bacterial surface that result in bacterial damage and destruction.

Our recent work with MRSA has shown the advantages of AFM in determining the antimicrobial and synergic capacities of biosurfactants and glycolipids in particular when combined with antibiotics. The project will investigate whether biosurfactant and antibiotic combinations can be effective in eliminating enterococcal biofilms.

The project builds upon a series of successful PhD projects within the Microbiology group and consequently the majority of techniques to be used (DNA and RNA extraction, analysis and sequencing; q-RT-PCR gene expression analysis; antibiotic resistance profiling and bacterial conjugation assays) are well established and will be used alongside colorimetric assays and biofilm assays to study the synergic effects of biosurfactant and antibiotic combinations.

High resolution microscopy will allow us to determine changes in bacteria size and morphology and crucially AFM will allow us to study changes in local surface properties of the bacteria including stiffness and adhesion. Full training will be provided in these and other relevant techniques to enable the candidate to successfully complete the programme of research.

Tackling antibiotic resistance is a WHO priority that requires a multifaceted approach. One of our major problems is the lack of new antibiotic discovery and the decreasing efficacy of current antibiotics against biofilm producing bacteria. This project will answer the question as to how biosurfactants enhance the efficacy of antibiotics against antibiotic resistant bacteria.

This project will be based at Ulster's Nutrition Innovation Centre for Food and Health (NICHE) (Coleraine campus) and NIBEC (Belfast campus).

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Sound understanding of subject area as evidenced by a comprehensive research proposal
• Clearly defined research proposal detailing background, research questions, aims and methodology

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• Completion of Masters at a level equivalent to commendation or distinction at Ulster
• Experience using research methods or other approaches relevant to the subject domain
• Sound understanding of subject area as evidenced by a comprehensive research proposal
• Work experience relevant to the proposed project
• Publications record appropriate to career stage
• Experience of presentation of research findings
• A comprehensive and articulate personal statement
• Relevant professional qualification and/or a Degree in a Health or Health related area

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living