Novel peptides for diagnosis and treatment of antibiotic resistant bacteria

Summary

Enterococci, while part of a normal healthy microbiome, can also be significant human pathogens with an increasing role in Healthcare Associated Infection (HAI).

They are major contributors to infections in intensive care units being responsible for bloodstream infections, urinary tract infections and wound infections.

Antibiotic resistance, particularly to the drug vancomycin, is a major contributor to their pathogenicity. Enterococci can utilise a pheromone induced plasmid conjugation system for the transfer of plasmids encoding resistance genes into non-resistant cells (HGT).

The transfer of genes is initiated by binding of peptide pheromones to the plasmid containing bacteria namely Vancomycin Resistance Enterococci (VRE) which are subsequently taken up within the cell.

Peptide pheromones are encoded on the genomic material of Enterococci and they can produce more than one pheromone. Resistance conferring plasmids only induce conjugation in response to their corresponding pheromone.

Plasmids also encode other virulence factors making the treatment of such infections difficult. Harnessing the HGT system could aid in preventing an increase in antibiotic resistant bacteria.

Artificially synthesised peptide pheromones could be utilised by being bound to antibiotics as a novel therapeutic delivery option.

Theoretically the uptake of an antibiotic bound to a pheromone into VRE would allow direct transport of the antibiotic to the intracellular region inducing cell death.

This approach may be utilised to treat patients with antibiotic resistant Enterococci infections and support the One Health Agenda.

The project will use state of the art molecular techniques alongside conventional microbiological techniques and high powered imaging techniques including confocal, SEM and TEM.

Important Information: Applications for more than one PhD studentship are welcome, however if you apply for more than one PhD project within Biomedical Sciences, your first application on the system will be deemed your first-choice preference and further applications will be ordered based on the sequential time of submission.

If you are successfully shortlisted, you will be interviewed only on your first-choice application and ranked accordingly. Those ranked highest will be offered a PhD studentship.

In the situation where you are ranked highly and your first-choice project is already allocated to someone who was ranked higher than you, you may be offered your 2nd or 3rd choice project depending on the availability of this project.

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
• A comprehensive and articulate personal statement

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.

• First Class Honours (1st) Degree
• Completion of Masters at a level equivalent to commendation or distinction at Ulster
• Practice-based research experience and/or dissemination
• Experience using research methods or other approaches relevant to the subject domain
• Work experience relevant to the proposed project
• Publications record appropriate to career stage
• Experience of presentation of research findings

Equal Opportunities

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.

Appointment will be made on merit.

Funding and eligibility

This project is funded by:

• Department for the Economy (DfE)

This scholarship will cover tuition fees and provide a maintenance allowance of £21,000* (tbc) per annum for three years (subject to satisfactory academic performance).  A Research Training Support Grant (RTSG) of approximately £900 per annum is also available.

To be eligible for these scholarships, applicants must meet the following criteria:

• Be a UK National, or

• Have settled status, or

• Have pre-settled status, or

• Have indefinite leave to remain or enter, or

• be an Irish National

Applicants should also meet the residency criteria which requires that they have lived in the EEA, Switzerland, the UK or Gibraltar for at least the three years preceding the start date of the research degree programme.

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.

*Part time PhD scholarships may be available, based on 0.5 of the full time rate, and will require a six year registration period