Novel strategy to tackle multidrug-resistant Staphylococcus aureus. (360G-Wellcome-107988_Z_15_Z)
Our preliminary data suggested mannitol-1-phosphate-5-dehydrogenase, a key enzyme in the mannitol pathway in Streptococcus aureus, as a promising therapeutic target, which is not subject to the antibiotic-resistant mechanism of the bacterium. To develop this hypothesis into a major project, we propose a research project aimed at validating our concept also in multidrug-resistant Streptococcus aureus, and characterising mannitol-1-phosphate dehydrogenase biochemically and structurally. To fulfil this aim, we will achieve following specific objectives: 1. Validation of the mannitol-1-phosphate-5-dehydrogenase as a novel target in multidrug-resistant Streptococcus aureus; 2. Kinetic characterisation of mannitol-1-phosphate-5-dehydrogenase; 3. Determination of the X-ray crystal structure of the free enzyme and complex with substrates or inhibitors to provide a framework for the inhibitor development; 4. Preliminary screening of commercial and open access inhibitor libraries as a basis for further inhibitor development. At the end of the project, we will have sufficient data and strong rationale that will place us in positon to stage a main project directed at developing a general strategy that exploits the inhibition of mannitol-1-phosphate-5-dehydrogenase for treating multidrug-resistant pathogens.
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Grant Details
Amount Awarded | 99613 |
Applicant Surname | Lee |
Approval Committee | ERG5 Pathogen Biology and Disease Transmission |
Award Date | 2015-04-28T00:00:00+00:00 |
Financial Year | 2014/15 |
Grant Programme: Title | Seed Award in Science |
Internal ID | 107988/Z/15/Z |
Lead Applicant | Dr Seung Lee |
Partnership Value | 99613 |
Planned Dates: End Date | 2018-02-28T00:00:00+00:00 |
Planned Dates: Start Date | 2015-09-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |