Does quorum sensing diversity affect cell-cell communication, biofilm fitness and susceptibility to antimicrobials?. (360G-Wellcome-088614_Z_09_Z)
If our ability to treat infection effectively is to continue, our understanding of the mechanisms through which current antibiotic therapies are subverted must be improved. Chronic lung infection with Pseudomonas aeruginosa (PA) is primarily responsible for the accelerated decline in lung function and mortality in patients with cystic fibrosis. Quorum sensing (QS) is a cell-cell communication system used by PA to regulate virulence and biofilm maturation: an attractive target for novel antim icrobial therapies. However, it is known that QS mutants arise during chronic lung infection. How phenotypically diverse are these mutants and do they influence the clinical status of the patient? This multidisciplinary proposal will utilise a combination of molecular techniques, animal models and social evolution theory to (1) determine the level of QS diversity in patients; (2) explore the effect of QS diversity on biofilm formation, pathogenesis in chronic lung infection and antimicrobial susceptibility; (3) develop and empirically test evolutionary theory to determine why this diversity arises and (4) assess the potential of QS as an antimicrobial target. The insights this work will provide could be instrumental in guiding future development and use of novel antimicrobials that disrupt PA virulence, thus increasing the efficacy of old and new antibiotics.
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Grant Details
Amount Awarded | 287073 |
Applicant Surname | Forrester |
Approval Committee | Clinical Interview Committee |
Award Date | 2009-07-09T00:00:00+00:00 |
Financial Year | 2008/09 |
Grant Programme: Title | Research Training Fellowship |
Internal ID | 088614/Z/09/Z |
Lead Applicant | Dr Doug Forrester |
Partnership Value | 287073 |
Planned Dates: End Date | 2016-02-29T00:00:00+00:00 |
Planned Dates: Start Date | 2010-04-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East Midlands |
Sponsor(s) | Prof Alan Knox, Prof Paul Williams |