The acquisition of additional control over quorum sensing regulation reduces the variability of final cell density in Burkholderia.

Bacteria usually possess more than one quorum sensing (QS) regulatory modules that sometimes form complex regulatory networks. These configurations have evolved through the integration of novel transcription factors into the native regulatory systems. However, the selective advantages provided by these alternative configurations on QS-related phenotypes is poorly predictable only based on their underlying network structure. Here, we show that the acquisition of extra regulatory modules of QS has important consequences on the overall regulation of microbial growth by significantly reducing the variability in the final cell density in Burkholderia. By mapping the distribution of horizontally transferred QS modules in extant bacterial genomes, we found that these tend to add up to already-present modules in the majority of cases. We then selected a strain harboring two intertwined QS modules and, using mathematical modeling, we predicted an intrinsic ability of the newly acquired module to buffer the variability in the final cell density. We validated this prediction choosing one strain possessing both systems, deleting one of the two and measuring parameters such as cell density and QS synthase promoter activity. Finally, using transcriptomics, we show that the de-regulation of metabolism likely plays a key role in differentiating the two configurations.