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CMBB Quorum Sensing Blockers Recent years have witnessed a rapid progress in our understanding of the role and extent of intercellular quorum sensing signalling in bacteria; the use of a chemical language for the colonisation of new surfaces, on man-made as well as on living surfaces. Important human pathogens, such as the bacteria that cause cholera, tuberculosis and cystic fibrosis (CF) possess communication systems to facilitate their colonisation of surfaces and for expression of virulence traits. The acylated homoserine lactone (AHL) signalling circuit in Gram negative bacteria is an important example. Thus, Pseudomonas aeruginosa employs two AHL systems for the colonisation and biofilm formation of lung tissue in CF patients. P. aeruginosa also expresses a range of AHL dependent virulence traits. If the signalling systems can be disrupted, it should be possible to stop the bacterium from colonising surfaces and causing disease. Such an inhibition acts through the specific interference with a signalling system, without affecting growth or killing the cell and hence without leading to the development of resistance, as is currently the case for most antimicrobial technologies. Furanones are structurally very similar to bacterial AHLs and we have shown that they specifically inhibit this regulatory system in a number of bacteria including marine strains. The compounds act at the LuxR homologous receptor proteins in these systems interfering with the binding of the bacterial AHLs. On this basis, furanones are leading candidates for a range of natural product based quorum sensing blockers. The main antibiofilm technology in the CMBB is based on the use of quorum sensing blockers. Lead QSBs have been trialed and demonstrated to be effective in a range of applications for the prevention and removal of unwanted biofilms. These include industrial applications, such as water treatment and filtration, industrial cleaners and the removal of biofilms from household surfaces. CMBB is also engaged in projects aimed at the prevention and removal of biofilms in medical conditions, including those of gum disease (gingivitis), P. aeruginosa lung tissue infections, and infections derived from catheters and ocular lenses. Specific ongoing projects include: |
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