Delineating the antimicrobial resistome of Clostridioides difficile

Clostridioides difficile (C. diff) is an important human pathogen, responsible for life-threatening intestinal infection in both hospital and community settings. Exacerbating the clinical impact of this organism, there is growing resistance to the antibiotics used to treat the infections it causes. Unfortunately, our understanding of the molecular mechanisms of antimicrobial resistance (AMR) in this species lags behind that for other major pathogens; whilst a number of resistance determinants have been defined to date, our knowledge of the C. diff resistome remains far from comprehensive.

This project seeks to dramatically increase our knowledge of AMR in C. diff, not only by identifying novel genetic determinants underlying resistance, but also by beginning to unravel the molecular detail of the encoded mechanisms. The potential benefits of gaining such knowledge are manifold, including building a more robust foundation for molecular AMR surveillance and providing strategic intelligence that could be exploited for producing the next generation of anti-C. diff antibiotics.

To achieve this, we will leverage access to one of Europe’s largest collections of C. diff isolates held at Leeds, which currently comprises several thousand well-characterized isolates. In the first instance, we will use bioinformatics to identify novel/potential resistance determinants in whole genome sequencing data, which will then undergo validation in molecular cloning experiments. Where such approaches are insufficient to define the genetic basis for resistance, we will use techniques such as functional metagenomics to physically ‘capture’ genes that confer AMR. Novel antibiotic resistance mechanisms will progress to structural and functional characterization, using approaches that the O’Neill lab are well versed in.

Collectively, these studies will deliver key insights into the genetic basis and mechanisms of AMR in an increasingly-important human pathogen.

Eligibility: 

You should hold a first degree equivalent to at least a UK upper-second class honours degree or a MSc degree in a relevant subject.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Biological Sciences minimum requirements in IELTS and TOEFL tests are:

• British Council IELTS - score of 6.0 overall, with no element less than 5.5
• TOEFL iBT - overall score of 87 with the listening and reading element no less than 20, writing element no less than 21 and the speaking element no less than 22.

How to apply:

To apply for this project applicants should complete an online application form and attach the following documentation to support their application. 

• a full academic CV
• degree certificate and transcripts of marks
• Evidence that you meet the University's minimum English language requirements (if applicable).
• Evidence of funding

To help us identify that you are applying for this project please ensure you provide the following information on your application form;

• Select PhD in Biological Sciences as your programme of study
• Give the full project title and name the supervisors listed in this advert