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)

£139,298

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