Combination therapy of quorum sensing inhibitors and biofilm blockers for the treatment of Pseudomonas aeruginosa infection in those with cystic fibrosis. (360G-Wellcome-092295_Z_10_Z)
We shall test the hypothesis that a combination approach to quorum sensing inhibition of Pseudomonas aeruginosa (PA)will provide a new therapeutic strategy for the treatment of lung infection in Cystic Fibrosis. PA uses semi-hierarchical QS pathways to maximise its virulence and defence through AHL and AQ signal mediated co-ordinated behaviour. Garlic can block the AHL-mediated QS regulon. To increase the completeness of QS inhibition we propose to also inhibit QS at the AQ level and block t he effect of a QS regulated product, lectins. Individually garlic, AQ precursor analogues and lectin inhibitors may all interfere with QS pathways at different points. The objectives are: 1) To investigate the effect of combinations of quorum sensing inhibitors (garlic, anthranilate derivatives) and lectin inhibitors (sugars and related dendrimers) upon P. aeruginosa biofilm formation and it s susceptibility to antibiotics. 2) To investigate the impact combinations of these inhibitors have on the biology of P. aeruginosa at the transcriptomic level. 3) To investigate the conservation of this effect on single and mixed biofilms of clinical P. aeruginosa cystic fibrosis isolates. . 4) To investigate the effect of these combined treatments on the virulence of P. aeruginosa in an insect larval infection model.
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Grant Details
Amount Awarded | 139298 |
Applicant Surname | Hurley |
Approval Committee | Clinical Interview Committee |
Award Date | 2010-07-15T00:00:00+00:00 |
Financial Year | 2009/10 |
Grant Programme: Title | Research Training Fellowship |
Internal ID | 092295/Z/10/Z |
Lead Applicant | Dr Matthew Hurley |
Partnership Value | 139298 |
Planned Dates: End Date | 2013-12-31T00:00:00+00:00 |
Planned Dates: Start Date | 2010-09-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East Midlands |
Sponsor(s) | Prof Alan Knox, Prof Paul Williams |