Biofilms4 International Conference edition:4 location:Winchester, UK date:1-3 September 2010
Salmonella is an important cause of foodborne infections worldwide. A major difficulty in the battle against Salmonella is the fact that Salmonella can form biofilms on various biotic and abiotic surfaces, both in- and outside the host. Therefore, the inhibition of these biofilms could be an effective way to combat Salmonella.
We are currently conducting a high-throughput screening (using the ‘Calgary Biofilm device’) of a compound library consisting of > 20.000 small molecules, in search of Salmonella biofilm inhibitors which are active at a broad temperature range and therefore have potential to be used both in- and outside the host.
The compounds have a molecular weight between 200 and 500 dalton and are selected on their possible drug ability. The screening is executed both at 16 °C and 37 °C. We aim at identifying compounds that inhibit biofilm formation, without killing the bacteria. This way, the development of resistance is less likely.
After screening of 16.000 compounds (80%), we identified 133 possible biofilm inhibitors. Subsequently the dose-response relationship of the ‘hits’ was determined, as well as the growth-influences of the compounds. The compounds with maximum biofilm inhibitory capacities and minimal growth influences, were studied further, both on prevention and destruction of biofilms from Salmonella and Pseudomonas. Using these results we identified 8 ‘lead’ families off which the “structure-activity relationship” will be determined aswell as the activity in different in vitro and in vivo testsystems. Finally the ‘Mode of Action’ of will be determined using reportergene studies and/or microarray analysis.