Chemical probes of bacterial signal transduction reveal that repellents stabilize and attractants destabilize the chemoreceptor array

The signal transduction cascade responsible for bacterial chemotaxis serves as a model for understanding how cells perceive and respond to their environments. Bacteria react to chemotactic signals by migrating toward attractants and away from repellents. Recent data suggest that the amplification of attractant stimuli depends on receptor collaboration: occupied and unoccupied chemoreceptors act together to relay attractant signals. Attractant signal transmission, therefore, depends on the organization of the chemoreceptors into a lattice of signaling proteins. The importance of this lattice for transducing repellent signals was unexplored. Here, we investigate the role of inter-receptor communication on repellent responses in Escherichia coli. Previously, we found that multivalent displays of attractants are more potent than their monovalent counterparts. To examine the importance of the chemoreceptor lattice in repellent signaling, we synthesized ligands displaying multiple copies of the repellent leucine. Monomeric leucine and low-valency leucine-displaying polymers were sensed as repellents. In contrast, multivalent displays of leucine capable of binding multiple chemoreceptors function not as potent repellents but as attractants. Intriguingly, chemical cross-linking studies indicate that these multivalent ligands, like monovalent attractants, disrupt the cellular chemoreceptor lattice. Thus, repellents stabilize the intrinsic chemoreceptor lattice, and attractants destabilize it. These results indicate that signals can be transmitted with high sensitivity via the disruption of protein-protein interactions. Moreover, our data demonstrate that repellents can be transformed into attractants merely by their multivalent display. These results have implications for designing agonists and antagonists for other signaling systems.