RT Journal Article SR Electronic T1 Bacterial quorum sensing allows graded and bimodal cellular responses to variations in population density JF bioRxiv FD Cold Spring Harbor Laboratory SP 850297 DO 10.1101/850297 A1 Jennifer B. Rattray A1 Stephen A. Thomas A1 Yifei Wang A1 Evgeniya Molotkova A1 James Gurney A1 John J. Varga A1 Sam P. Brown YR 2021 UL http://biorxiv.org/content/early/2021/11/10/850297.abstract AB Quorum sensing (QS) is a mechanism of cell–cell communication that connects gene expression to environmental conditions (e.g. density) in many bacterial species, mediated by diffusible signal molecules. Current functional studies focus on a dichotomy of QS on/off (or, quorate / sub-quorate) states, overlooking the potential for intermediate, graded responses to shifts in the environment. Here, we track QS regulated protease (lasB) expression and show that Pseudomonas aeruginosa can deliver a graded behavioral response to fine-scale variation in population density, on both the population and single-cell scales. On the population scale, we see a graded response to variation in environmental population density. On the single-cell scale, we see significant bimodality at higher densities, with separate OFF and ON sub-populations that respond differentially to changes in density; static OFF cells and increasing intensity of expression among ON cells. While the QS-controlled behavioral output is graded, the underlying multi-signal dynamics display a threshold shift in signal concentration with increasing density, reflecting the onset of positive signal auto-regulation at intermediate densities. Together these results indicate that QS can tune gene expression to graded environmental change, with no critical cell mass or ‘quorum’ at which behavioral responses are activated on either the individual cell or population scale. In an infection context, our results indicate there is not a hard threshold separating sub-quorate ‘stealth’ mode and a quorate ‘attack’ mode.Competing Interest StatementThe authors have declared no competing interest.