Chemical cooperation and information warfare between species

Quorum sensing enables unicellular organisms to coordinate their behavior and function in such a way that they can adapt to changing environments and compete, as well as coexist, with multicellular organisms. Pseudomonas aeruginosa is an opportunistic pathogen that causes disease in immunocompromised patients. Quorum sensing in this pathogen is mediated by binding of the transcriptional activator, LasR, to its ligand 3-oxo-C12-HSL, leading to biofilm formation and secretion of virulence factors. We are targeting QS in P. aeruginosa and other bacteria with various chemical tools, such as a set of electrophilic probes that are designed to bind LasR covalently, leading to inhibition of QS regulated gene expression. These probes can be used as molecular tools to obtain new insights into the mechanisms of activation and deactivation of bacterial quorum sensing. Furthermore, we recently found that certain QS molecules and other natural products can also directly affect the behavior of other bacterial species as well as that of eukaryotes. Diverse eukaryotes have been found to react strongly to the presence of these compounds (often initiating counter-warfare to jam bacterial communication), and such phenomena indicate that chemical communication within and between species plays a crucial role in guiding cooperation and competition between species.