Welcome to the AEROPATH web site
The project has now been completed after four years of funding and we have submitted our final report to the Commission.Our project successfully identified and assessed novel drug targets in P. aeruginosa, discovered novel hit compounds with the potential to pave the way towards new and urgently needed antibiotics. Specifically -
- More than 35 k.o. mutants were constructed representing one of the largest number of such precise gene deletions in P. aeruginosa.
- A mouse lung model of P. aeruginosa infection was established and mutants tested for virulence and capacity to survive.
- The project has shown that early detailed biochemical assessment of proteins is essential if they are to be screened for inhibitors. The results are available for other researchers to use with over 39 new structures and 100 diffraction data sets of ligand complexes being deposited in the public domain.
- An assay that supports compound screening for the fatty acid biosynthetic pathway and that can be widely applied to other pathogens was devised.
- The structural information generated together with the functional characterisation of the compounds derived from virtual and fragment-based screening approaches formed a sound basis for the assessment of the targets.
- The incorporation of chemogenomics/structural information was used to annotate the PAO1 genome providing an assessment of druggability. This offers an unprecedented look at a genome in terms of where potential drug targets might exist. The data provides confidence in some targets, but clearly marks others as difficult if not un-druggable. Critically, the assessment suggests that there exist several new areas of research that might be exploited in antibiotic drug discovery and sets a benchmark for annotation of pathogen genomes.
We generated a wide variety of resources and a significant body of data. These are documented at this site, have been placed in public domain databases or published. Access the AEROPATH Target Database at http://aeropath.lifesci.dundee.ac.uk/ and the results of the targets we assessed at http://aeropath.lifesci.dundee.ac.uk/aeropath_projects.