SELF-SIGNALING BY A NATIVE QUORUM SENSING SYSTEM IN BACILLUS SUBTILIS

Quorum sensing (QS) is a bacterial cell-cell communication system, where cells secrete a diffusible signal molecule that accumulates in the external environment and interact with a cognate receptor, to activate a variety of responses in a density-dependent manner. QS response is therefore considered to be cell non-autonomous, with the signal affecting all cells in the community equally (in `trans`). Theoretically, however, a signal-producing cell should have a higher concentration level around it than the environmental average concentration, leading to additional, cell-autonomous, self-sensing and activation in `cis`. Sensing of self-produced signals by cells can limit their ability to sense cell density. The extent of such self-signaling has not been explored in a natural system yet. We studied the existence of self-signaling in the native B. subtilis ComQXPA QS system. In this system the ComX modified peptide signal is cleaved and modified by ComQ. It activates the membranal histidine kinase receptor ComP which subsequently phosphorylates ComA, a transcription factor that regulates diverse behaviors. By co-culture experiments, we find that signal-producing cells have a higher signal response than a corresponding non-producing mutants that still respond to the extracellular signal. We show that this cell-autonomous response requires the presence of ComQ, ComX and ComP. We utilized genetic analysis to rule out a specific intracellular regulatory effect of ComQ or ComX on reception level. Finally, we show that signal-producing cells respond as if they have a constant added signal over the non-producing cells, in agreement with the predictions of self-signaling. Our results therefore support the existence of self-signaling in a native quorum sensing system, and indicate that self-signaling constrain the dynamical range over which cells can sense population density.