Endogenous metabolite modulates protein-protein interactions in Escherichia coli*

Indole, an interspecies and inter-kingdom signaling molecule, is produced by various species of bacteria. Indole regulates several aspects of bacterial physiology, including cell division, motility, and chemotaxis. We hypothesize that these diverse regulatory roles likely arise due to indole’s ability to regulate intracellular protein-protein interactions and molecular motor functions. In this work, we studied the influence of indole on the functioning of a large, multimeric protein complex-the flagellar motor-in E. coli. We monitored the response of individual motors in live cells upon treatment with indole. The response was consistent with a model where the conformations of component protein subunits flipped due to the metabolite, indicating that indole likely reduces the free energy differences between the tensed and relaxed states of individual proteins in the complex. Measurements also revealed decrease in membrane potential due to indole. We employed an Ising-based to quantify the effects of indole on motor functions. Our calculations suggest that indole decreases nearest neighbor interactions in multi-subunit complexes within the motor. We show that these regulatory properties of indole control E. coli’s motility and their ability to colonize surfaces.