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Divide and conquer: disrupting bacterial biofilms with cyclic dipeptides (360G-Wellcome-210486_Z_18_Z)

By 2050 10 million lives could be claimed a year by drug resistant infections. We must develop new strategies for antimicrobial drugs. Often in infections bacteria form biofilms, requiring concentrations of antibiotics up to 1000 fold higher to be treated. Cyclic dipeptides are molecules produced by organisms in all domains of life, and their function is unknown. They can inhibit bacterial growth and/or biofilm formation, albeit by undetermined mechanisms. The majority of the biological effects caused by cyclic dipeptides are inter-species and in some instances inter-kingdom, mediating host pathogen interactions. I will study enzymes from gram-positive and gram-negative bacteria involved in the production of different cyclic dipeptides. I will characterise each enzyme biochemically and structurally and determine their substrate scope. I will produce novel molecules, which will be used to disrupt growth and biofilm formation in Pseudomonas aeruginosa and Staphylococcus aureus growing alone and in bacterial co-cultures. I will combine genetic and chemoproteomic approaches to determine the molecular targets of cyclic dipeptides in P. aeruginosa and S. aureus. I will validate targets using bacterial mutants and biochemical assays. The identification of molecular targets of cyclic dipeptides will unveil crucial pathways for inter-species interactions and identify novel antimicrobial targets and molecules.

£1,016,218

21 Feb 2018

Grant details
Amount Awarded 1016218
Applicant Surname Czekster
Approval Committee Sir Henry Dale Fellowship Interview Committee
Award Date 2018-02-21T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Sir Henry Dale Fellowship
Internal ID 210486/Z/18/Z
Lead Applicant Dr Clarissa Czekster
Planned Dates: End Date 2023-06-01T00:00:00+00:00
Planned Dates: Start Date 2018-06-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland
Sponsor(s) Prof Clare Peddie, Prof David Evans
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