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Delineating the antimicrobial resistome of Clostridioides difficile


Key facts

Type of research degree
Application deadline
Ongoing deadline
Country eligibility
International (open to all nationalities, including the UK)
Professor Alex O'Neill
Additional supervisors
Dr Jane Freeman
<h2 class="heading hide-accessible">Summary</h2>

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.

<h2 class="heading hide-accessible">Full description</h2>

<p>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.</p> <p>To achieve this, we will leverage access to one of Europe&rsquo;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 &lsquo;capture&rsquo; genes that confer AMR. Novel antibiotic resistance mechanisms will progress to structural and functional characterization, using approaches that the O&rsquo;Neill lab are well versed in.</p> <p>Collectively, these studies will deliver key insights into the genetic basis and mechanisms of AMR in an increasingly-important human pathogen.&nbsp;</p> <p>References</p> <ul> <li>Wilson DN, Hauryliuk V, Atkinson GC, O&#39;Neill AJ (2020) Target protection as a key antibiotic resistance mechanism. Nat Rev Microbiol. 18: 637-648.&nbsp;</li> <li>Kime L, Randall CP, Banda FI, Coll F, Wright J, Richardson J, Empel J, Parkhill J, O&#39;Neill AJ (2019) Transient Silencing of Antibiotic Resistance by Mutation Represents a Significant Potential Source of Unanticipated Therapeutic Failure. mBio. 10: e01755-19.&nbsp;</li> <li>Freeman J, Vernon J, Pilling S, Morris K, Nicolson S, Shearman S, Clark E, Palacios-Fabrega JA, Wilcox M: Pan-European Longitudinal Surveillance of Antibiotic Resistance among Prevalent Clostridium difficile Ribotypes&rsquo; Study Group (2020) Five-year Pan-European, longitudinal surveillance of Clostridium difficile ribotype prevalence and antimicrobial resistance: the extended ClosER study. Eur J Clin Microbiol Infect Dis. 39: 169-177.</li> </ul>

<h2 class="heading">How to apply</h2>

<p>To apply for this project applicants should complete an <a href="">online application form</a> and attach the following documentation to support their application.&nbsp;</p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks</li> <li>Evidence that you meet the University&#39;s minimum English language requirements (if applicable).</li> <li>Evidence of funding</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Biological Sciences as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. &nbsp;Within the Faculty/School of &laquo;Name&raquo; we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+; and people with disabilities. Applicants will always be selected based on merit and ability.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

<h2 class="heading heading--sm">English language requirements</h2>

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<h2 class="heading">Funding on offer</h2>

<p>This project is available to applicants who are able to self-fund their studies, or who have a sponsor to cover these costs.</p>

<h2 class="heading">Contact details</h2>

<p>For further information please contact the Faculty Graduate School<br /> e:&nbsp;<a href=""></a>,&nbsp;</p>