PLANTS AS A RICH SOURCE OF BACTERIAL BEHAVIOR MODULATORS

Quorum sensing (QS) is a mechanism by which bacteria can act as a single multicellular organism and coordinate wide gene expression based on cell-density. In order to achieve this, bacteria secrete small diffusible signal molecules called autoinducers which stimulates regulation of gene expression that is beneficial to the whole community. Understanding quorum sensing (QS) mechanisms at the highest possible molecular detail is essential for solving challenges caused by bacterial virulence and biofilm formation.

The plant pathogen Agrobacterium tumefaciens and the opportunistic human pathogen Pseudomonas aeruginosa are two of many gram negative bacteria that use a QS mechanism to produce their virulence factors. A. tumefaciens induces the formation of crown gall tumors at the wound sites of host plants, while P. aeruginosa, targets immune-compromised patients, causing severe infections. These two bacteria use the intensely studied LuxI/LuxR-like QS system to preform gene regulation, therefore attenuation of QS will enable us to control the infection process.

To accomplish this goal we performed a library screening of 3800 natural compounds in order to find potential agonists and antagonists. Several highly potent molecules were selected and a focused library of analogs around these hits was synthesized and screened. We are currently performing infection assays on possible target plants of A. tumefaciens in the presence of most active compounds. Using these tools, we aim to gain a significant advance in understanding QS mechanisms in both A. tumefaciens and P. aeruginosa.