A biofilm is a community-based microbial lifestyle with a distinctively high capacity to tolerate antibiotics. Biofilms are now recognized as the main cause of chronically untreatable bacterial infections in humans but no specific anti-biofilm drugs yet exist. Here we will search for inhibitors of the collective communication system that makes possible the formation of biofilms, termed as Quorum Sensing, especially in gram-negative bacteria. Quorum Sensing Inhibitors (QSI) are emerging as the ideal anti-biofilm drugs. They reduce bacterial virulence without killing the cells, they are selective towards bacterial cells and can enhance antibiotics efficacy. We recently discovered QSI of natural origin that interfere with the LuxI/LuxR Quorum Sensing system at low micromolar potencies. In this application we will further develop these hit compounds via a concerted strategy combining QSI research with medicinal chemistry and computational studies. These efforts will be in turn expanded to discover other new QSI scaffolds, and further characterize them on in vivo infective models. To our knowledge, this would be the first-of-its-kind effort in Finland to discover novel QSI compounds to target clinically relevant biofilms infections.
|Effective start/end date||01/01/2017 → 31/12/2019|