In search of Broad Applicable, Small Molecule Inhibitors of Salmonella Biofilm Formation

Salmonella is one of the most important causes 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. Biofilms are multicellular structures, in which the bacteria live in a self-produced gel-like matrix. Within these biofilms, Salmonella is protected against a wide range of environmental influences such as desiccation, antibiotics, disinfectants and the immune system. As such, biofilm formation is an important survival strategy of Salmonella, both in- and outside the host. Therefore, the prevention and/or eradication of these biofilms could be an effective way to limit the spread of Salmonella. Our laboratory has previously identified a potent group of Salmonella biofilm inhibitors. A drawback of these compounds is that they only seem to be active at temperatures below 25 °C. Therefore, we are currently conducting a high-throughput screening (using the 'Calgary Biofilm device') of a compound library, consisting of 17.000 small molecules, in search for Salmonella biofilm inhibitors which are active at a temperature ranging from 16 °C till 37 °C, and therefore have potential to be used both in- and outside the host. The library contains a broad range of compounds, selected on their possible drug ability. The compounds have a molecular weight between 200 and 500 dalton and the screening is executed both at 16 °C and 37 °C. We aim at identifying compounds that inhibit biofilm formation, but that do not kill the bacteria. In this way, the development of resistance, which is a major drawback of classical antibiotics, is less likely. As such, these biofilm inhibitors could be a sustainable alternative in the production of safe and healthy food. After the screening of the first ±1800 compounds, we already found 47 possible biofilm inhibitors, of which 37 are active at 16 °C and 10 at 37 °C. None of those inhibitors are active at both temperatures but these preliminary results indicate it will probably be possible to indentify new broad applicable Salmonella biofilm inhibitors using this assay.