Infections associated with the employment of urinary catheters and intravenous cannulae are a common cause of hospitalisation, illness and premature death (Chant et al 2011). A single episode of cannula-related septicaemia has been estimated, in the USA, to cost in excess of $10,000 (Warren et al, 2006). Thus, the clinical problem that this project addresses is enormous. The cost of catheter- and cannula-related infections is significant not only in health-care related costs, such as prolonged in-patient stay, but also in blocked catheters requiring urgent hospital admission and increased mortality in intensive care units in patients with septicaemia resulting from infected intravenous cannulae. There is increasing clinical research interest in bacterial biofilm formation on implantable medical devices. Such biofilms are often resistant to conventional antibiotics (Hetrick and Schoenfisch 2006), causing serious illness and failure of the device (e.g. catheter blockage).
This project will apply recent developments in our understanding of the antimicrobial role of NO, together with our studies of the capacity of acidified nitrite to release NO (Duncan et al 1995; Zhang et al 1998; Hardwick et al 2001; Lundberg et al 2004; Gilchrist et al 2010). Acidification of nitrite is now known to be an important mechanism by which NO is generated in the gut and skin of mammals to prevent infection. In addition to inhibiting adherence and growth of pathogenic bacteria, NO powerfully inhibits the activation of blood platelets and thereby prevents blood clotting. This property may well be useful in improving the antithrombotic inner surface of polymer arterial grafts which are made from Dacron or PTFE (polytetrafluoroethylene; Teflon).
The aim of the project is to use this method of NO generation to confer antimicrobial activity to medical devices made from, or coated with, polymers. We have already shown that acidified nitrite can be incorporated into a silicone polymer which will release NO when exposed to water. One exciting aspect of this technology is that it can, in theory, be applied to a large number of different polymers and would therefore need little alteration in the production line of existing plastic medical devices such as catheters, cannulae and implantable devices. An ability to manufacture NO-releasing plastics, that are resistant to the growth of microbial biofilms, could provide a revolutionary solution to the ever-increasing and serious issue of infections associated with medical device implantation. The aim of the project will be to establish: (a) that NO-releasing polymers of several types can be manufactured; (b) the optimum NO release to inhibit the growth of bacterial biofilms.
The supervisory team is uniquely placed, in terms of expertise and the availability of facilities - for biophysical testing of NO diffusion through plastics, for in vitro research, e.g. cell culture and ozone-based chemiluminescence for the detection of NO (full facilities in the IBCS St Luke’s laboratories), and clinical facilities at the RD&E, including the NIHR Clinical Research Facility.
Suitable Candidates may have backgrounds in Bioscience, Biomedical Science, Biochemistry, Microbiology, Chemistry, Physics, Materials Science, or related subjects.
For more information about the project and informal enquiries, please contact the primary supervisor: Professor Paul Winyard: [email protected]
Information about current fees: https://www.exeter.ac.uk/pg-research/money/fees/
Information about possible funding sources: http://www.exeter.ac.uk/pg-research/money/alternativefunding/
Information about Doctoral Loans: http://www.exeter.ac.uk/pgresearch/money/phdfunding/postgraduatedoctoralloans/
Chant C, Smith OM, Marshall JC, Friedrich JO (2011) Critical Care Med 39, 1167-73.
Duncan C, Dougal H, Johnston P, Green S, Brogan R, Leifert C, Smith L, Golden M, Benjamin N (1995) Nature Med 1, 546-51.
Gilchrist M, Winyard PG, Benjamin (2010) Nitric Oxide 22, 104-109.
Hardwick JBJ, Tucker AT, Wilks M, Johnston A and Benjamin N (2001) Clin Sci 100, 395–400.
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Warren DK, Quadir WW, Hollenbeak CS, Elward AM, Cox MJ, Fraser VJ (2006) Crit Care Med. 34, 2084-89
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