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Quorum Sensing Blockers and Anti-biofilm Technologies

Recent years have witnessed a rapid progress in our understanding of the role and extent of intercellular quorum sensing signalling in bacteria. Many bacteria communicate using chemicals which facilitate colonisation of new surfaces, on man-made as well as on living surfaces. This includes important human pathogens, such as the bacteria that cause cholera, tuberculosis and cystic fibrosis (CF). These bacteria possess communication systems that facilitate their colonisation of surfaces and their expression of virulence traits. The acylated homoserine lactone (AHL) signalling circuit in Gram negative bacteria is one such important communication system. For example, Pseudomonas aeruginosa employs two AHL systems for the colonisation and biofilm formation on lung tissue in CF patients. P. aeruginosa also expresses a range of AHL dependent virulence traits.
 
The need to prevent biofilm formation and expression of virulence traits, in a range of bacterial species, has led to the search for quorum sensing blockers. If these signal systems can be disrupted, it should be possible to stop the bacterium from colonising surfaces and causing disease. Such inhibition acts through specific interference with a signalling system, without affecting growth or killing the cell and hence without leading to the development of resistance, a major downside for most current antimicrobial technologies.
 
One key antibiofilm technology in the CMB is based on the use of furanones as quorum sensing blockers (QSBs). Furanones are structurally very similar to bacterial AHLs and we have shown that they specifically inhibit this regulatory system in a number of bacteria. The compounds act as competitive inhibitors, preventing the AHL signal from binding its cognate receptor and therefore, keeps the QS system in an uninduced state.
 
Synthetic furanones have been trialled and demonstrated to be effective in a range of applications for the prevention and removal of unwanted biofilms. CMB is engaged in projects aimed at the prevention and removal of biofilms in medical conditions, including P. aeruginosa lung tissue infections, and infections derived from catheters and contact lenses. Projects targeted at industrial applications include water treatment and filtration, industrial cleaners and the prevention of microbial corrosion in gas and oil pipelines. Commercialisation of furanones as inhibitors of biofilms is now being progressed through Biosignal Ltd. (ASX:BOS).
 

For any queries on this project please contact Dr. Nicolas Barraud