Efficacy of novel antimicrobial treatments on oral pathogens

Project details:

Bacterial oral infections can cause a variety of problems including dental caries, abscesses, gingivitis and periodontal disease. Severe periodontal disease is thought to affect 19% of the global population, approximately 1 billion cases. Periodontitis can have major effects including damage and loss of supportive tissue around the tooth leading to development of inaccessible pockets and bone loss. Furthermore, periodontitis is also a risk factor for infective endocarditis. To compound these problems, antimicrobial resistance (AMR) is rapidly increasing and is a major global health problem. With 1 in 10 antibiotic prescriptions attributable to dental care in the UK alone, large increases in AMR have been observed in the oral microbiota which is now considered a reservoir for distribution of AMR mechanisms. This inexorable increase in AMR coupled with large numbers of cases, which are expensive to treat, demonstrates a major public health burden with a clear need for the development of novel therapeutics.

The tetraspanins, a superfamily of human cell membrane proteins, associate with multiple human proteins to form dynamic structured islands, or tetraspanin-enriched microdomains (TEMs), which are utilised by bacteria to adhere to and enter cells. The tetraspanins have been shown to associate with various proteins hijacked by bacterial pathogens to enter adhere to and enter host cells, including integrins and proteoglycans. We have previously demonstrated that blockade of the tetraspanin CD9, using a variety of methods, reduces adherence of multiple bacteria to human epithelial cells by >50%. However, CD9 does not act as a receptor and appears to organise and cluster the required host proteins required for adhesion at the cell membrane. This strongly suggests that despite the use of different host receptors in different cells a general mechanism of bacterial adherence exists which utilises CD9. Together, this raises crucial questions; does CD9 organise various bacterial receptors across cell types to facilitate infection and can this be exploited to devise novel antimicrobial treatments?

This project would use 2D and 3D models to investigate this phenomenon and explore the effects of our novel antimicrobial treatments on both commensal and pathogenic bacteria within the oral microbiome. The proposed project intends to investigate the role of CD9 in bacterial oral infections, provide the first characterisation of ‘adhesion platforms’ organised by CD9 which facilitate the adhesion of oral pathogens and provide proof of concept that disruption of these platforms with CD9 disrupting agents can reduce infection and ease the burden on antibiotics.

Entry Requirements:

Candidates must have a first or upper second class honours degree with significant research experience.

How to apply:

Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select School of Clinical Dentistry as the department.