An organelle-tethering mechanism couples flagellation to cell division in bacteria

In both free-living and pathogenic bacteria, problems in the synthesis and assembly of early flagellar components invariably lead to cell division defects. However, the mechanism that fine-tunes the cell division cycle with the flagellar biogenesis is poorly understood. Herein, we report the role of the conserved regulator MadA in coupling flagellar biogenesis to cell division in Caulobacter crescentus. We demonstrate that MadA is required to induce the flagellar specific type III export component FlhA to release and activate FliX, which in-turn is required to license the conserved σ54-activator, FlbD. In the absence of MadA, FliX is tethered to FlhA, inhibiting FlbD activation and crippling completion of flagellar biogenesis and cell division. Furthermore, we demonstrate that MadA exploits a divisome-stoichiometric to control cell division. We propose that MadA has a sentinel-type function that warrants progression of the flagellar biogenesis, and the cell division cycle, once early flagellar structures are properly assembled. Global transcriptome profiling (gene expression) by RNA-Seq in Caulobacter crescentus NA1000(WT), flbD::Tn and ΔmadA backgrounds.