FlhDFlhC

FlhD and FlhC are two bacterial proteins that together form a master regulator complex, commonly referred to as FlhDC, which initiates the gene expression cascade for flagellar biosynthesis in many proteobacteria, including Escherichia coli and Salmonella enterica. The FlhDC complex acts as a transcriptional activator that directly stimulates class II flagellar operons, setting the stage for assembly of the basal body, hook, and subsequent production of the flagellum.

Function and regulatory cascade. FlhDC activates promoters of class II genes, which encode components of the flagellar apparatus and the sigma factor FliA (sigma28). Activation of FliA controls class III genes that encode later-stage components such as flagellin. The regulatory pathway therefore coordinates a sequential assembly process, ensuring that structural components are produced in the correct order and that flagellar synthesis proceeds only when appropriate.

Regulation and control. FlhDC activity is finely regulated at multiple levels. Expression of the flhDC operon responds to environmental signals and global regulatory networks, and FlhDFlhC can be modulated by proteolysis (Lon protease) and by RNA-based and protein-based regulators. In some bacteria, additional factors such as YdiV can inhibit FlhDC activity or its engagement with target promoters, contributing to species- and condition-specific control. Repression by chromosomal factors such as H-NS and activation by cyclic AMP receptor protein–cAMP signaling have also been described in different contexts.

Distribution and significance. FlhDFlhC is conserved across many Gram-negative bacteria and is central to motility and environmental sensing. Disruption of FlhDC typically results in loss or substantial reduction of motility due to failure to express the flagellar gene hierarchy, while altered regulation can lead to hyper- or hypo-flagellation. The complex thus serves as a key integrator of cellular state and flagellar assembly.