Peptide signaling without feedback in signal production operates as a true quorum sensing communication system in Bacillus subtilis.

Bacterial quorum sensing (QS) is based on signal molecules (SM), which increase in concentration with cell density. At critical SM concentration, a variety of adaptive genes sharply change their expression from basic level to maximum level. In general, this sharp transition, a hallmark of true QS, requires an SM dependent positive feedback loop, where SM enhances its own production. Some communication systems, like the peptide SM-based ComQXPA communication system of Bacillus subtilis, do not have this feedback loop and we do not understand how and if the sharp transition in gene expression is achieved. Based on experiments and mathematical modeling, we observed that the SM peptide ComX encodes the information about cell density, specific cell growth rate, and even oxygen concentration, which ensure power-law increase in SM production. This enables together with the cooperative response to SM (ComX) a sharp transition in gene expression level and this without the SM dependent feedback loop. Due to its ultra-sensitive nature, the ComQXPA can operate at SM concentrations that are 100–1000 times lower than typically found in other QS systems, thereby substantially reducing the total metabolic cost of otherwise expensive ComX peptide. Iztok Dogsa et al. use mathematical modeling and experimental approaches to investigate how the ComQXPA communication system in Bacillus subtilis initiate a quorum-sensing response without the positive feedback loop dependent on signal molecules seen in many systems. They find that the peptide ComX encodes information about cell density, specific cell growth rate and oxygen concentration, which ensure power-law increase in signal molecule production and enables a sharp transition in gene expression level without the typical feedback loop.