Selection of Appropriate Autoinducer Analogues for the Modulation of Quorum Sensing at the Host-Bacterium Interface

Bacteria regulate a variety of phenotypes in response to their population density using quorum sensing (QS). This phenomenon is regulated by small molecule or peptide signals, the best characterized of which are the N-acyl l-homoserine lactones (AHLs) utilized by Gram-negative bacteria. As many QS-controlled phenotypes, notably pathogenicity and symbiosis, can profoundly impact host eukaryotes, there is significant interest in developing methods for modulating QS signaling and either ameliorating or augmenting these phenotypes. One strategy has been the use of non-native AHL analogues to agonize or antagonize specific AHL receptors. This approach is complicated, however, by the potential for prospective hosts to respond to both native AHLs and synthetic analogues. Accordingly, identifying AHL analogues with little or no activity toward eukaryotes is important in developing QS modulation as a strategy for the regulation of prokaryotic behaviors. Herein, we utilize the model plant Arabidopsis thaliana to characterize eukaryotic responses to a variety of synthetic AHL analogues to identify structural elements of existing scaffolds that may elicit responses in prospective hosts. Our results indicate that, while many of these compounds have no discernible effect on A. thaliana, some elicit strong phenotypes similar to those produced by auxin, a hormone involved in almost all aspects of plant development. We outline concentrations and chemical scaffolds that are ideal for deployment on plant hosts for the regulation of QS. This approach should be exportable to other eukaryotes for the selection of optimal AHL tools for the study of QS at the host-microbe interface.