Plant Biofilm Inhibitors to Discover Biofilm Genes

Abstract : To control biofilms, we have synthesized the natural biofilm inhibitor (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone from the red alga Delisea pulchra and determined that it functions by disrupting quorum sensing in Vibrio harveyi by blocking all three channels of the V. harveyi quorum sensing system by rendering the quorum sensing master regulator protein LuxR unable to bind to the promoter sequences of quorum sensing-regulated genes. We have also discovered other inhibitors of cell signaling including indole, hydroxy indoles, and fluorouracil. We found indole is an interspecies signal that decreases E. coli biofilms through SdiA and increases the biofilms of pseudomonads. Importantly, we found that indole reduces the virulence of P. aeruginosa by decreasing quorum sensing phenotypes. In addition, we discovered uracil is a new second messenger in the cell which led to the discovery the fluorouracil is a potent anti-biofilm and anti-virulence compound. We also determined the role of prophage in the biofilm formation of E. coli, focused on toxin/antitoxins systems to show how they are related to persister cell formation and to show for the first time they are related to biofilm formation, and engineered some biofilm regulators so that biofilm formation may be controlled by rewiring cellular metabolism.