A quorum of mechano-sensing fungal consortia

Bacteria use Quorum sensing (QS) to coordinate gene expression in dense cell populations. Here, we show that eukaryote S. Cerevisiae uses an alternative strategy, the quorum mechano-sensing (QMS), to resolve growth conflicts in the fungal consortia. QMS connects the biomechanical signal perception through adhesin FLO11 and transmembrane histidine kinase SLN1, triggering an intracellular signaling cascade for the cell density-dependent regulation of gene expression. Both cis and trans interactions of FLO11 are required for the inhibition of SLN1 and involve the extracellular fibronectin type III-like domain of FLO11. Genetic deletion of FLO11 removes inhibition of SLN1, associated with the spontaneous activation of gene expression whereas overproduction of FLO11 strengthens the inhibitory effect of FLO11 on SLN1. Therefore, adjusting the amount of FLO11 directly scales with the level of SLN1 inhibition, forecasting the outcome of growth competition at the macroscopic scale. Furthermore, the integration of an orthogonal synthetic circuit downstream of SLN1 allows for QMS-controlled regulation of gene expression in cell populations. Our study reveals a molecular pathway connecting FLO11 adhesion to SLN1-dependent intracellular regulation of gene expression in fungi. FLO11 and SLN1 coordinate kin recognition and growth conflict resolution through gene expression in dense fungal populations. This study challenges the classical view of chemically-driven QS and provides new strategies for controlling population growth through quorum mechano-sensing.